BRCA1 Comprehensive Gene Annotation for Clinical Genetic Testing

BRCA1 is critical for hereditary breast/ovarian cancer genetic testing. For a comprehensive gene annotation used in clinical reporting: 1. How many …

BRCA1 is critical for hereditary breast/ovarian cancer genetic testing. For a comprehensive gene annotation used in clinical reporting: 1. How many transcripts both in ensembl and refseq? How many exons in the canonical? 2. How many UniProt entries? What domains (InterPro)? 3. How many PDB structures exist? What experimental methods? 4. How many ClinVar variants? How many pathogenic? 5. What Reactome pathways involve BRCA1? 6. AI variant predictions: How many SpliceAI splice-altering predictions exist? How many AlphaMissense missense pathogenicity scores? Show variants with scores. IMPORTANT: LIST ALL THE ITEMS, AT LEAST THE FIRST 50 RECORDS FOR EACH CATEGORY.

Structured Data Sources

This answer was generated using Claude Opus 4.5 + BioBTree MCP, querying 12 biological databases.

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphamissense, clinvar, ensembl, exon, hgnc, interpro, pdb, reactome, refseq, spliceai, transcript, uniprot

Generated: 2026-03-26 — For the latest data, query BioBTree directly via MCP or API.

View API calls (25)

search(BRCA1) https://sugi.bio/biobtree/api/search?i=BRCA1
entry(HGNC:1100, hgnc) https://sugi.bio/biobtree/api/entry?i=HGNC%3A1100&s=hgnc
search(BRCA1, ensembl) https://sugi.bio/biobtree/api/search?i=BRCA1&s=ensembl
entry(ENSG00000012048, ensembl) https://sugi.bio/biobtree/api/entry?i=ENSG00000012048&s=ensembl
map(ENSG00000012048, >>ensembl>>transcript) https://sugi.bio/biobtree/api/map?i=ENSG00000012048&m=%3E%3Eensembl%3E%3Etranscript
map(ENSG00000012048, >>ensembl>>refseq) https://sugi.bio/biobtree/api/map?i=ENSG00000012048&m=%3E%3Eensembl%3E%3Erefseq
map(ENSG00000012048, >>ensembl>>refseq) https://sugi.bio/biobtree/api/map?i=ENSG00000012048&m=%3E%3Eensembl%3E%3Erefseq
entry(ENST00000357654, transcript) https://sugi.bio/biobtree/api/entry?i=ENST00000357654&s=transcript
map(ENST00000357654, >>transcript>>exon) https://sugi.bio/biobtree/api/map?i=ENST00000357654&m=%3E%3Etranscript%3E%3Eexon
map(ENSG00000012048, >>ensembl>>uniprot) https://sugi.bio/biobtree/api/map?i=ENSG00000012048&m=%3E%3Eensembl%3E%3Euniprot
map(ENSG00000012048, >>ensembl>>refseq) https://sugi.bio/biobtree/api/map?i=ENSG00000012048&m=%3E%3Eensembl%3E%3Erefseq
entry(P38398, uniprot) https://sugi.bio/biobtree/api/entry?i=P38398&s=uniprot
map(P38398, >>uniprot>>interpro) https://sugi.bio/biobtree/api/map?i=P38398&m=%3E%3Euniprot%3E%3Einterpro
map(P38398, >>uniprot>>pdb) https://sugi.bio/biobtree/api/map?i=P38398&m=%3E%3Euniprot%3E%3Epdb
map(HGNC:1100, >>hgnc>>clinvar) https://sugi.bio/biobtree/api/map?i=HGNC%3A1100&m=%3E%3Ehgnc%3E%3Eclinvar
map(ENSG00000012048, >>ensembl>>reactome) https://sugi.bio/biobtree/api/map?i=ENSG00000012048&m=%3E%3Eensembl%3E%3Ereactome
map(HGNC:1100, >>hgnc>>spliceai) https://sugi.bio/biobtree/api/map?i=HGNC%3A1100&m=%3E%3Ehgnc%3E%3Espliceai
map(HGNC:1100, >>hgnc>>clinvar[germline_classification=="Pathogenic"]) https://sugi.bio/biobtree/api/map?i=HGNC%3A1100&m=%3E%3Ehgnc%3E%3Eclinvar%5Bgermline_classification%3D%3D%22Pathogenic%22%5D
map(HGNC:1100, >>hgnc>>spliceai) https://sugi.bio/biobtree/api/map?i=HGNC%3A1100&m=%3E%3Ehgnc%3E%3Espliceai
map(ENST00000357654, >>transcript>>alphamissense) https://sugi.bio/biobtree/api/map?i=ENST00000357654&m=%3E%3Etranscript%3E%3Ealphamissense
map(ENST00000357654, >>transcript>>alphamissense) https://sugi.bio/biobtree/api/map?i=ENST00000357654&m=%3E%3Etranscript%3E%3Ealphamissense
map(HGNC:1100, >>hgnc>>spliceai[score>=0.8]) https://sugi.bio/biobtree/api/map?i=HGNC%3A1100&m=%3E%3Ehgnc%3E%3Espliceai%5Bscore%3E%3D0.8%5D
map(HGNC:1100, >>hgnc>>clinvar[germline_classification=="Pathogenic"]) https://sugi.bio/biobtree/api/map?i=HGNC%3A1100&m=%3E%3Ehgnc%3E%3Eclinvar%5Bgermline_classification%3D%3D%22Pathogenic%22%5D
map(ENST00000357654, >>transcript>>alphamissense[am_class=="likely_pathogenic"]) https://sugi.bio/biobtree/api/map?i=ENST00000357654&m=%3E%3Etranscript%3E%3Ealphamissense%5Bam_class%3D%3D%22likely_pathogenic%22%5D
map(HGNC:1100, >>hgnc>>spliceai[score>=0.8]) https://sugi.bio/biobtree/api/map?i=HGNC%3A1100&m=%3E%3Ehgnc%3E%3Espliceai%5Bscore%3E%3D0.8%5D

BRCA1

BRCA1 Comprehensive Gene Annotation for Clinical Reporting Gene Overview

Attribute	Value
HGNC ID	HGNC:1100
Symbol	BRCA1
Name	BRCA1 DNA repair associated
Ensembl Gene	ENSG00000012048
Location	17q21.31 (chr17:43,044,292-43,170,245, minus strand)
Biotype	Protein-coding
Aliases	RNF53, BRCC1, PPP1R53, FANCS

Transcripts Ensembl Transcripts: 47 total

#	Transcript ID	Biotype	Start	End
1	ENST00000357654	protein_coding	43044295	43125364
2	ENST00000352993	protein_coding	43044295	43125370
3	ENST00000471181	protein_coding	43044295	43125483
4	ENST00000461574	protein_coding	43044304	43125370
5	ENST00000468300	protein_coding	43044805	43125451
6	ENST00000470026	protein_coding	43044304	43125343
7	ENST00000473961	protein_coding	43044295	43125364
8	ENST00000476777	protein_coding	43044298	43125360
9	ENST00000477152	protein_coding	43044295	43125364
10	ENST00000478531	protein_coding	43044295	43125359
11	ENST00000484087	protein_coding	43045434	43125343
12	ENST00000489037	protein_coding	43044295	43125321
13	ENST00000491747	protein_coding	43045678	43125356
14	ENST00000493795	protein_coding	43045629	43125402
15	ENST00000493919	protein_coding	43044295	43125402
16	ENST00000494123	protein_coding	43044295	43125450
17	ENST00000497488	protein_coding	43044295	43125300
18	ENST00000586385	protein_coding	43045563	43125329
19	ENST00000591534	protein_coding	43045563	43125329
20	ENST00000591849	protein_coding	43045563	43125329
21	ENST00000618469	protein_coding	43044304	43125364
22	ENST00000634433	protein_coding	43044295	43170245
23	ENST00000644379	protein_coding	43045086	43125364
24	ENST00000644555	protein_coding	43044304	43125370
25	ENST00000652672	protein_coding	43044295	43125483
26	ENST00000700182	protein_coding	43070344	43125343
27	ENST00000713676	protein_coding	43044304	43125343
28	ENST00000899954	protein_coding	43044805	43125483
29	ENST00000921914	protein_coding	43044292	43125476
30	ENST00000921915	protein_coding	43044295	43125367
31	ENST00000921916	protein_coding	43044304	43125360
32	ENST00000945268	protein_coding	43044299	43125410
33	ENST00000945269	protein_coding	43044824	43125487
34	ENST00000354071	retained_intron	43091098	43125315
35	ENST00000472490	retained_intron	43067274	43071066
36	ENST00000700081	retained_intron	43044302	43050409
37	ENST00000700082	retained_intron	43044981	43048473
38	ENST00000700083	retained_intron	43104225	43106139
39	ENST00000700184	retained_intron	43099643	43124339
40	ENST00000461221	nonsense_mediated_decay	43045678	43125288
41	ENST00000461798	nonsense_mediated_decay	43099831	43125370
42	ENST00000492859	nonsense_mediated_decay	43094112	43125300
43	ENST00000642945	nonsense_mediated_decay	43094482	43125343
44	ENST00000700183	nonsense_mediated_decay	43094033	43125343
45	ENST00000621897	protein_coding_CDS_not_defined	43076488	43082760
46	ENST00000700185	protein_coding_CDS_not_defined	43114391	43125370
47	ENST00000700186	protein_coding_CDS_not_defined	43122343	43125370

RefSeq Transcripts: 759 total (showing first 50)

#	RefSeq ID	Type	Status	MANE Select
1	NM_001407571	mRNA	REVIEWED	false
2	NM_001407581	mRNA	REVIEWED	false
3	NM_001407582	mRNA	REVIEWED	false
4	NM_001407583	mRNA	REVIEWED	false
5	NM_001407585	mRNA	REVIEWED	false
6	NM_001407587	mRNA	REVIEWED	false
7	NM_001407590	mRNA	REVIEWED	false
8	NM_001407591	mRNA	REVIEWED	false
9	NM_001407593	mRNA	REVIEWED	false
10	NM_001407594	mRNA	REVIEWED	false
11	NM_001407596	mRNA	REVIEWED	false
12	NM_001407597	mRNA	REVIEWED	false
13	NM_001407598	mRNA	REVIEWED	false
14	NM_001407602	mRNA	REVIEWED	false
15	NM_001407603	mRNA	REVIEWED	false
16	NM_001407605	mRNA	REVIEWED	false
17	NM_001407610	mRNA	REVIEWED	false
18	NM_001407611	mRNA	REVIEWED	false
19	NM_001407612	mRNA	REVIEWED	false
20	NM_001407613	mRNA	REVIEWED	false
21	NM_001407614	mRNA	REVIEWED	false
22	NM_001407615	mRNA	REVIEWED	false
23	NM_001407616	mRNA	REVIEWED	false
24	NM_001407617	mRNA	REVIEWED	false
25	NM_001407618	mRNA	REVIEWED	false
26	NM_001407619	mRNA	REVIEWED	false
27	NM_001407620	mRNA	REVIEWED	false
28	NM_001407621	mRNA	REVIEWED	false
29	NM_001407622	mRNA	REVIEWED	false
30	NM_001407623	mRNA	REVIEWED	false
31	NM_001407624	mRNA	REVIEWED	false
32	NM_001407625	mRNA	REVIEWED	false
33	NM_001407626	mRNA	REVIEWED	false
34	NM_001407627	mRNA	REVIEWED	false
35	NM_001407628	mRNA	REVIEWED	false
36	NM_001407629	mRNA	REVIEWED	false
37	NM_001407630	mRNA	REVIEWED	false
38	NM_001407631	mRNA	REVIEWED	false
39	NM_001407632	mRNA	REVIEWED	false
40	NM_001407633	mRNA	REVIEWED	false
41	NM_001407634	mRNA	REVIEWED	false
42	NM_001407635	mRNA	REVIEWED	false
43	NM_001407636	mRNA	REVIEWED	false
44	NM_001407637	mRNA	REVIEWED	false
45	NM_001407638	mRNA	REVIEWED	false
46	NM_001407639	mRNA	REVIEWED	false
47	NM_001407640	mRNA	REVIEWED	false
48	NM_001407641	mRNA	REVIEWED	false
49	NM_001407642	mRNA	REVIEWED	false
50	NM_001407644	mRNA	REVIEWED	false

Canonical Transcript Exons: 23 exons (ENST00000357654)

#	Exon ID	Start	End	Strand
1	ENSE00001852567	43125271	43125364	-
2	ENSE00003559512	43124017	43124115	-
3	ENSE00003510592	43115726	43115779	-
4	ENSE00003541068	43106456	43106533	-
5	ENSE00003531836	43104868	43104956	-
6	ENSE00001917948	43104122	43104261	-
7	ENSE00004011563	43099775	43099880	-
8	ENSE00004011550	43097244	43097289	-
9	ENSE00004011558	43090944	43091032	-
10	ENSE00004011559	43095846	43095922	-
11	ENSE00004011566	43091435	43094860	-
12	ENSE00004011560	43082404	43082575	-
13	ENSE00004011561	43076488	43076614	-
14	ENSE00004011562	43074331	43074521	-
15	ENSE00004011554	43070928	43071238	-
16	ENSE00004011556	43067608	43067695	-
17	ENSE00004011567	43063333	43063373	-
18	ENSE00004011565	43063874	43063951	-
19	ENSE00004011551	43057052	43057135	-
20	ENSE00004011553	43051063	43051117	-
21	ENSE00004011568	43049121	43049194	-
22	ENSE00004011552	43047643	43047703	-
23	ENSE00004011564	43044295	43045802	-

2. UniProt Entries: 22 total Canonical Entry: P38398

Attribute	Value
UniProt ID	P38398
Name	Breast cancer type 1 susceptibility protein
Alt Names	RING finger protein 53, RING-type E3 ubiquitin transferase BRCA1
Length	1,863 amino acids
Mass	207,721 Da

All UniProt Entries

#	UniProt ID
1	P38398 (canonical)
2	A0A0U1RRA9
3	A0A2R8Y6Y9
4	A0A2R8Y7V5
5	A0A494C182
6	A0A8V8TPY7
7	A0A9Y1QPT7
8	A0A9Y1QQK3
9	C6YB45
10	C9IZW4
11	E7ENB7
12	E7EQW4
13	E7EUM2
14	E7EWN5
15	E9PC22
16	G1UI37
17	H0Y850
18	H0Y8B8
19	H0Y8D8
20	K7EJW3
21	K7EPC7
22	Q3B891

InterPro Domains: 9 domains

#	InterPro ID	Name	Type
1	IPR001357	BRCT_dom	Domain
2	IPR001841	Znf_RING	Domain
3	IPR011364	BRCA1	Family
4	IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
5	IPR017907	Znf_RING_CS	Conserved_site
6	IPR018957	Znf_C3HC4_RING-type	Domain
7	IPR025994	BRCA1_serine_dom	Domain
8	IPR031099	BRCA1-associated	Family
9	IPR036420	BRCT_dom_sf	Homologous_superfamily

3. PDB Structures: 33 total

#	PDB ID	Title	Method	Resolution
1	1JM7	Solution structure of the BRCA1/BARD1 RING-domain heterodimer	SOLUTION NMR	-
2	1JNX	Crystal structure of the BRCT repeat region from BRCA1	X-RAY DIFFRACTION	2.5 Å
3	1N5O	Structural consequences of a cancer-causing BRCA1-BRCT missense mutation	X-RAY DIFFRACTION	2.8 Å
4	1OQA	Solution structure of the BRCT-c domain from human BRCA1	SOLUTION NMR	-
5	1T15	Crystal Structure of Brca1 BRCT Domains with phosphorylated BACH1	X-RAY DIFFRACTION	1.85 Å
6	1T29	BRCA1 BRCT repeats bound to a phosphorylated BACH1 peptide	X-RAY DIFFRACTION	2.3 Å
7	1T2U	BRCA1 missense variant V1809F	X-RAY DIFFRACTION	2.8 Å
8	1T2V	Structural basis of phospho-peptide recognition by BRCT domain	X-RAY DIFFRACTION	3.3 Å
9	1Y98	BRCT repeats of BRCA1 bound to a CtIP phosphopeptide	X-RAY DIFFRACTION	2.5 Å
10	2ING	BRCA1 BRCT mutant M1775K	X-RAY DIFFRACTION	3.6 Å
11	3COJ	BRCA1 BRCT with phosphorylated peptide from Acetyl-CoA Carboxylase 1	X-RAY DIFFRACTION	3.21 Å
12	3K0H	BRCA1 BRCT with minimal recognition tetrapeptide (amidated)	X-RAY DIFFRACTION	2.7 Å
13	3K0K	BRCA1 BRCT with minimal recognition tetrapeptide (free carboxy)	X-RAY DIFFRACTION	2.7 Å
14	3K15	BRCA1 BRCT D1840T with tetrapeptide (amidated)	X-RAY DIFFRACTION	2.8 Å
15	3K16	BRCA1 BRCT D1840T with tetrapeptide (free carboxy)	X-RAY DIFFRACTION	3.0 Å
16	3PXA	BRCA1 BRCT missense G1656D	X-RAY DIFFRACTION	2.55 Å
17	3PXB	BRCA1 BRCT missense T1700A	X-RAY DIFFRACTION	2.5 Å
18	3PXC	BRCA1 BRCT missense R1699Q	X-RAY DIFFRACTION	2.8 Å
19	3PXD	BRCA1 BRCT missense R1835P	X-RAY DIFFRACTION	2.8 Å
20	3PXE	BRCA1 BRCT missense E1836K	X-RAY DIFFRACTION	2.85 Å
21	4IFI	BRCA1 BRCT with BAAT peptide	X-RAY DIFFRACTION	2.2 Å
22	4IGK	BRCA1 BRCT with ATRIP peptide	X-RAY DIFFRACTION	1.75 Å
23	4JLU	BRCA1 BRCT with doubly phosphorylated Abraxas	X-RAY DIFFRACTION	3.5 Å
24	4OFB	BRCA1 BRCT with nonphosphopeptide inhibitor	X-RAY DIFFRACTION	3.05 Å
25	4U4A	BRCA1 BRCT with singly phospho Abraxas	X-RAY DIFFRACTION	3.51 Å
26	4Y18	BRCA1 BRCT with Abraxas double phosphorylated peptide	X-RAY DIFFRACTION	3.5 Å
27	4Y2G	BRCA1 BRCT with Abraxas single phosphorylated peptide	X-RAY DIFFRACTION	2.5 Å
28	6G2I	ACC-BRCT filament structure	ELECTRON MICROSCOPY	5.9 Å
29	7JZV	BRCA1-UbcH5c/BARD1 E3-E2 module bound to nucleosome	ELECTRON MICROSCOPY	3.9 Å
30	7LYB	Nucleosome with BRCA1-BARD1-UbcH5c	ELECTRON MICROSCOPY	3.28 Å
31	8GRQ	BRCA1/BARD1 bound to H2AK127-UbcH5c-Ub nucleosome	ELECTRON MICROSCOPY	3.87 Å
32	8RS8	BRCA1 BRCTs with RIF1 phosphopeptide	X-RAY DIFFRACTION	1.31 Å
33	9QPX	BRCA1 BRCT with RNA polymerase II pSer5-CTD peptide	X-RAY DIFFRACTION	3.0 Å

Experimental Methods Summary:

X-ray Diffraction: 28 structures
Electron Microscopy (Cryo-EM): 4 structures
Solution NMR: 2 structures

4. ClinVar Variants Total Variants: 15,445 Pathogenic Variants: >2,500 (showing representative 50)

#	ClinVar ID	Variant	Type	Classification	Review Status
1	125465	c.882del (p.Asp295fs)	Deletion	Pathogenic	Reviewed by expert panel
2	125477	c.902_903insT (p.Lys301fs)	Insertion	Pathogenic	Reviewed by expert panel
3	125481	c.984_985insC (p.Asn329fs)	Insertion	Pathogenic	Reviewed by expert panel
4	125486	c.1101_1102insC (p.Glu368fs)	Insertion	Pathogenic	Reviewed by expert panel
5	125488	c.1129dup (p.Ser377fs)	Duplication	Pathogenic	Reviewed by expert panel
6	125491	c.19_47del (p.Arg7fs)	Deletion	Pathogenic	Reviewed by expert panel
7	125495	c.1356del (p.Glu453fs)	Deletion	Pathogenic	Reviewed by expert panel
8	125499	c.1392dup (p.Tyr465fs)	Duplication	Pathogenic	Reviewed by expert panel
9	125500	c.1440_1441insA (p.Leu481fs)	Insertion	Pathogenic	Reviewed by expert panel
10	125501	c.1462dup (p.Thr488fs)	Duplication	Pathogenic	Reviewed by expert panel
11	125503	c.1518del (p.Arg507fs)	Deletion	Pathogenic	Reviewed by expert panel
12	125504	c.1561_1562delinsTA (p.Ala521Ter)	Indel	Pathogenic	Reviewed by expert panel
13	125507	c.1695dup (p.Lys566fs)	Duplication	Pathogenic	Reviewed by expert panel
14	125508	c.1700dup (p.Asn567fs)	Duplication	Pathogenic	Reviewed by expert panel
15	125511	c.70_71insA (p.Cys24Ter)	Insertion	Pathogenic	Reviewed by expert panel
16	125512	c.70_71insTGTC (p.Cys24fs)	Insertion	Pathogenic	Reviewed by expert panel
17	125513	c.1812del (p.Ala605fs)	Deletion	Pathogenic	Reviewed by expert panel
18	125516	c.80+1G>C	SNV	Pathogenic	Multiple submitters
19	125517	c.80+1G>T	SNV	Pathogenic	Multiple submitters
20	125518	c.80+2T>G	SNV	Pathogenic	Multiple submitters
21	125519	c.80+4A>T	SNV	Pathogenic	Reviewed by expert panel
22	125528	c.1893_1894insT (p.Ser632Ter)	Insertion	Pathogenic	Reviewed by expert panel
23	125532	c.2038_2039insCC (p.Lys680fs)	Insertion	Pathogenic	Reviewed by expert panel
24	125535	c.2077_2078insTA (p.Asp693fs)	Insertion	Pathogenic	Reviewed by expert panel
25	125539	c.2098_2099insA (p.Leu700fs)	Insertion	Pathogenic	Reviewed by expert panel
26	125542	c.2188dup (p.Glu730fs)	Duplication	Pathogenic	Reviewed by expert panel
27	125546	c.2214del (p.Val740fs)	Deletion	Pathogenic	Reviewed by expert panel
28	125547	c.2215_2216insCT (p.Lys739fs)	Insertion	Pathogenic	Reviewed by expert panel
29	125548	c.2217dup (p.Val740fs)	Duplication	Pathogenic	Reviewed by expert panel
30	125552	c.2273dup (p.Leu758fs)	Duplication	Pathogenic	Reviewed by expert panel
31	125555	c.2337_2338del (p.Gln780fs)	Deletion	Pathogenic	Reviewed by expert panel
32	125556	c.2355dup (p.Leu786fs)	Duplication	Pathogenic	Reviewed by expert panel
33	125560	c.2376del (p.Lys793fs)	Deletion	Pathogenic	Reviewed by expert panel
34	125567	c.135-2A>G	SNV	Pathogenic	Multiple submitters
35	125568	c.2438dup (p.Leu814fs)	Duplication	Pathogenic	Reviewed by expert panel
36	125570	c.139dup (p.Cys47fs)	Duplication	Pathogenic	Reviewed by expert panel
37	125571	c.2474dup (p.Asp825fs)	Duplication	Pathogenic	Reviewed by expert panel
38	125575	c.2586_2593del (p.Val863fs)	Deletion	Pathogenic	Reviewed by expert panel
39	125579	c.2658_2659insA (p.Ala887fs)	Insertion	Pathogenic	Reviewed by expert panel
40	125581	c.2686del (p.Ser896fs)	Deletion	Pathogenic	Reviewed by expert panel
41	125589	c.171del (p.Pro58fs)	Deletion	Pathogenic	Reviewed by expert panel
42	125590	c.2799del (p.Gln934fs)	Deletion	Pathogenic	Reviewed by expert panel
43	125593	c.2868del (p.Gln957fs)	Deletion	Pathogenic	Reviewed by expert panel
44	125594	c.2871_2872insA (p.Phe958fs)	Insertion	Pathogenic	Reviewed by expert panel
45	125595	c.2889_2890del (p.Gly964fs)	Deletion	Pathogenic	Reviewed by expert panel
46	125597	c.2995_2996delinsTA (p.Leu999Ter)	Indel	Pathogenic	Reviewed by expert panel
47	125601	c.3044dup (p.Asn1016fs)	Duplication	Pathogenic	Reviewed by expert panel
48	125603	c.3053_3054insTGAGA (p.Ile1019fs)	Microsatellite	Pathogenic	Reviewed by expert panel
49	125607	c.3114_3117delinsGA (p.Ala1039fs)	Indel	Pathogenic	Reviewed by expert panel
50	125609	c.3158_3159insG (p.Val1054fs)	Insertion	Pathogenic	Reviewed by expert panel

5. Reactome Pathways: 59 total

#	Pathway ID	Name	Disease
1	R-HSA-5693532	DNA Double-Strand Break Repair	No
2	R-HSA-5693538	Homology Directed Repair	No
3	R-HSA-5685942	HDR through Homologous Recombination (HRR)	No
4	R-HSA-5685938	HDR through Single Strand Annealing (SSA)	No
5	R-HSA-5693571	Nonhomologous End-Joining (NHEJ)	No
6	R-HSA-5693565	ATM-mediated phosphorylation at DNA double strand breaks	No
7	R-HSA-5693607	Processing of DNA double-strand break ends	No
8	R-HSA-5693579	Homologous DNA Pairing and Strand Exchange	No
9	R-HSA-5693616	Presynaptic phase of homologous DNA pairing	No
10	R-HSA-5693554	Resolution of D-loop through SDSA	No
11	R-HSA-5693568	Resolution of D-loop through Holliday Junctions	No
12	R-HSA-5693537	Resolution of D-Loop Structures	No
13	R-HSA-5693606	DNA Double Strand Break Response	No
14	R-HSA-5693567	HDR through HRR or SSA	No
15	R-HSA-69473	G2/M DNA damage checkpoint	No
16	R-HSA-69481	G2/M Checkpoints	No
17	R-HSA-69620	Cell Cycle Checkpoints	No
18	R-HSA-1640170	Cell Cycle	No
19	R-HSA-73894	DNA Repair	No
20	R-HSA-912446	Meiotic recombination	No
21	R-HSA-1221632	Meiotic synapsis	No
22	R-HSA-1500620	Meiosis	No
23	R-HSA-1474165	Reproduction	No
24	R-HSA-1266738	Developmental Biology	No
25	R-HSA-3700989	Transcriptional Regulation by TP53	No
26	R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes	No
27	R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	No
28	R-HSA-5633007	Regulation of TP53 Activity	No
29	R-HSA-8953750	Transcriptional Regulation by E2F6	No
30	R-HSA-212436	Generic Transcription Pathway	No
31	R-HSA-73857	RNA Polymerase II Transcription	No
32	R-HSA-74160	Gene expression (Transcription)	No
33	R-HSA-3108214	SUMOylation of DNA damage response proteins	No
34	R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	No
35	R-HSA-2990846	SUMOylation	No
36	R-HSA-8951664	Neddylation	No
37	R-HSA-5689901	Metalloprotease DUBs	No
38	R-HSA-5688426	Deubiquitination	No
39	R-HSA-597592	Post-translational protein modification	No
40	R-HSA-392499	Metabolism of proteins	No
41	R-HSA-9755511	KEAP1-NFE2L2 pathway	No
42	R-HSA-9711123	Cellular response to chemical stress	No
43	R-HSA-2262752	Cellular responses to stress	No
44	R-HSA-8953897	Cellular responses to stimuli	No
45	R-HSA-9825895	Regulation of MITF-M-dependent genes	No
46	R-HSA-9730414	MITF-M-regulated melanocyte development	No
47	R-HSA-9856651	MITF-M-dependent gene expression	No
48	R-HSA-9663199	Defective DNA double strand break response due to BRCA1 loss	Yes
49	R-HSA-9699150	Defective DSB response due to BARD1 loss	Yes
50	R-HSA-9701192	Defective HRR due to BRCA1 loss of function	Yes
51	R-HSA-9704331	Defective HDR through HRR due to PALB2 loss of BRCA1 binding	Yes
52	R-HSA-9704646	Defective HDR due to PALB2 loss of BRCA2/RAD51/RAD51C binding	Yes
53	R-HSA-9709570	Impaired BRCA2 binding to RAD51	Yes
54	R-HSA-9709603	Impaired BRCA2 binding to PALB2	Yes
55	R-HSA-9675135	Diseases of DNA repair	Yes
56	R-HSA-9675136	Diseases of DNA Double-Strand Break Repair	Yes
57	R-HSA-9701190	Defective HRR due to BRCA2 loss of function	Yes
58	R-HSA-9701193	Defective HRR due to PALB2 loss of function	Yes
59	R-HSA-1643685	Disease	Yes

6. AI Variant Predictions SpliceAI: 3,719 total predictions (50 high-score variants, score ≥0.8)

#	Variant	Effect	Score
1	17:43045800:TTG:T	acceptor_gain	1.00
2	17:43045801:TGCTG:T	acceptor_loss	1.00
3	17:43047713:C:CT	acceptor_gain	1.00
4	17:43047713:C:T	acceptor_gain	1.00
5	17:43047714:A:T	acceptor_gain	1.00
6	17:43049119:A:AC	donor_gain	1.00
7	17:43049120:C:CC	donor_gain	1.00
8	17:43049120:CTGTG:C	donor_gain	1.00
9	17:43049195:C:CC	acceptor_gain	1.00
10	17:43049195:CTAAA:C	acceptor_loss	1.00
11	17:43057046:CTTTA:C	donor_loss	1.00
12	17:43057047:TTTAC:T	donor_loss	1.00
13	17:43057048:TTACC:T	donor_loss	1.00
14	17:43057049:TACCT:T	donor_loss	1.00
15	17:43057050:ACCT:A	donor_loss	1.00
16	17:43057051:C:CG	donor_loss	1.00
17	17:43057051:CCTTT:C	donor_gain	1.00
18	17:43057131:TCATG:T	acceptor_gain	1.00
19	17:43057132:CATG:C	acceptor_gain	1.00
20	17:43057132:CATGC:C	acceptor_gain	1.00
21	17:43057133:ATG:A	acceptor_gain	1.00
22	17:43057134:TG:T	acceptor_gain	1.00
23	17:43057136:C:CA	acceptor_loss	1.00
24	17:43057136:C:CC	acceptor_gain	1.00
25	17:43057137:T:A	acceptor_loss	1.00
26	17:43070926:A:AC	donor_gain	1.00
27	17:43045798:AATTG:A	acceptor_gain	0.99
28	17:43045799:ATTG:A	acceptor_gain	0.99
29	17:43045801:TG:T	acceptor_gain	0.99
30	17:43045803:C:CC	acceptor_gain	0.99
31	17:43049112:AATAC:A	donor_loss	0.99
32	17:43049113:ATACT:A	donor_loss	0.99
33	17:43049114:TACTT:T	donor_loss	0.99
34	17:43049115:ACTTA:A	donor_loss	0.99
35	17:43049116:CT:C	donor_loss	0.99
36	17:43049117:TT:T	donor_loss	0.99
37	17:43049118:TA:T	donor_loss	0.99
38	17:43049119:ACTG:A	donor_loss	0.99
39	17:43049120:CT:C	donor_gain	0.99
40	17:43049120:CTG:C	donor_gain	0.99
41	17:43049120:CTGT:C	donor_gain	0.99
42	17:43049191:TGAT:T	acceptor_gain	0.99
43	17:43049200:A:AC	acceptor_gain	0.99
44	17:43057050:A:AC	donor_gain	0.99
45	17:43057051:C:CC	donor_gain	0.99
46	17:43057133:A:C	acceptor_gain	0.99
47	17:43063371:CCC:C	acceptor_gain	0.99
48	17:43063372:CCC:C	acceptor_gain	0.99
49	17:43063373:CCTAA:C	acceptor_loss	0.99
50	17:43063374:CTAAA:C	acceptor_loss	0.99

AlphaMissense: 12,463 total predictions (50 likely_pathogenic variants shown)

#	Variant	Protein Change	Score	Classification
1	17:43045761:A:G	W1837R	0.998	likely_pathogenic
2	17:43045761:A:T	W1837R	0.998	likely_pathogenic
3	17:43045747:A:C	S1841R	0.996	likely_pathogenic
4	17:43045747:A:T	S1841R	0.996	likely_pathogenic
5	17:43045749:T:G	S1841R	0.996	likely_pathogenic
6	17:43047684:A:T	V1809D	0.993	likely_pathogenic
7	17:43045759:C:A	W1837C	0.990	likely_pathogenic
8	17:43045759:C:G	W1837C	0.990	likely_pathogenic
9	17:43045772:A:T	V1833E	0.983	likely_pathogenic
10	17:43045751:T:A	D1840V	0.982	likely_pathogenic
11	17:43045760:C:G	W1837S	0.980	likely_pathogenic
12	17:43045752:C:G	D1840H	0.978	likely_pathogenic
13	17:43045757:A:T	V1838E	0.971	likely_pathogenic
14	17:43045766:C:G	R1835P	0.969	likely_pathogenic
15	17:43045751:T:G	D1840A	0.966	likely_pathogenic
16	17:43045743:C:G	A1843P	0.964	likely_pathogenic
17	17:43045742:G:T	A1843E	0.961	likely_pathogenic
18	17:43045751:T:C	D1840G	0.958	likely_pathogenic
19	17:43045745:A:T	V1842E	0.956	likely_pathogenic
20	17:43047687:A:T	V1808E	0.955	likely_pathogenic
21	17:43045748:C:A	S1841I	0.954	likely_pathogenic
22	17:43045750:G:C	D1840E	0.954	likely_pathogenic
23	17:43045750:G:T	D1840E	0.954	likely_pathogenic
24	17:43045752:C:A	D1840Y	0.948	likely_pathogenic
25	17:43045754:A:G	L1839S	0.941	likely_pathogenic
26	17:43045713:A:C	Y1853D	0.940	likely_pathogenic
27	17:43047684:A:C	V1809G	0.924	likely_pathogenic
28	17:43045737:A:C	Y1845D	0.918	likely_pathogenic
29	17:43045760:C:A	W1837L	0.914	likely_pathogenic
30	17:43047678:T:G	Q1811P	0.914	likely_pathogenic
31	17:43045763:T:A	E1836V	0.910	likely_pathogenic
32	17:43045761:A:C	W1837G	0.909	likely_pathogenic
33	17:43045748:C:T	S1841N	0.907	likely_pathogenic
34	17:43047677:C:A	Q1811H	0.903	likely_pathogenic
35	17:43047677:C:G	Q1811H	0.903	likely_pathogenic
36	17:43045739:A:G	L1844P	0.896	likely_pathogenic
37	17:43045764:C:T	E1836K	0.894	likely_pathogenic
38	17:43045752:C:T	D1840N	0.881	likely_pathogenic
39	17:43047670:C:G	A1814P	0.870	likely_pathogenic
40	17:43045713:A:G	Y1853H	0.867	likely_pathogenic
41	17:43045709:A:G	L1854P	0.867	likely_pathogenic
42	17:43045745:A:C	V1842G	0.866	likely_pathogenic
43	17:43047667:A:G	W1815R	0.865	likely_pathogenic
44	17:43047667:A:T	W1815R	0.865	likely_pathogenic
45	17:43045713:A:T	Y1853N	0.858	likely_pathogenic
46	17:43045754:A:C	L1839W	0.850	likely_pathogenic
47	17:43047681:A:T	V1810E	0.848	likely_pathogenic
48	17:43047678:T:C	Q1811R	0.843	likely_pathogenic
49	17:43045767:G:C	R1835G	0.837	likely_pathogenic
50	17:43047685:C:A	V1809F	0.834	likely_pathogenic

Summary Statistics

Category	Count
Ensembl Transcripts	47
RefSeq Transcripts	759
Exons (canonical ENST00000357654)	23
UniProt Entries	22
InterPro Domains	9
PDB Structures	33
ClinVar Variants (total)	15,445
ClinVar Pathogenic Variants	>2,500
Reactome Pathways	59
SpliceAI Predictions (total)	3,719
SpliceAI High-Impact (score ≥0.8)	~500
AlphaMissense Predictions (total)	12,463
AlphaMissense Likely Pathogenic	~1,500