# NM_002204.4(ITGA3):c.2299del

https://sugi.bio/variant/itga3-c-2299del

## Summary

**ITGA3 c.2299del** is classified **Likely pathogenic** in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-15). Associated with epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome.

**At a glance:** Likely pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the ITGA3 gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Infancy, Neonatal |
| Diagnostic panels | ITGA3 is a diagnostic-grade gene on 10 Genomics England panels |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0017377/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [ITGA3](https://sugi.bio/atlas/gene/ITGA3/) |
| Coding change (HGVS c.) | c.2299del |
| MANE Select transcript | [NM_002204](https://www.ncbi.nlm.nih.gov/nuccore/NM_002204) |
| Variant type | Deletion |
| Location | chr17:50078823-50078823 (GRCh38) |
| ClinVar | [VCV3582280](https://www.ncbi.nlm.nih.gov/clinvar/variation/3582280/) |

**All HGVS expressions:** `NC_000017.10:g.48156189del`, `NC_000017.11:g.50078825del`, `NG_029107.2:g.27850del`, `NM_002204.4:c.2299del`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 11.127, GERP 0.803, phastCons 1 — highly conserved position (PP3-type support)
- Non-coding constraint (Gnocchi): **Z 2.26**, o/e 0.84 (1 kb window 50,078,000–50,079,000). A higher Z means the window carries less variation than expected. Describes the 1 kb window, not this allele. No ClinGen expert panel references Gnocchi and no ACMG-calibrated threshold exists for it. *Descriptive; no cut-point applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**ITGA3** population constraint: LOEUF 0.69, pLI 2.2512e-10, missense-Z 2.7063. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 83.88, 45% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of ITGA3 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** ITGA3's established molecular role includes protease binding.


### Pathways affected {#pathways}

ITGA3 participates in **4 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Basigin interactions](https://reactome.org/content/detail/R-HSA-210991) | curated |
| [Laminin interactions](https://reactome.org/content/detail/R-HSA-3000157) | curated |
| [MET activates PTK2 signaling](https://reactome.org/content/detail/R-HSA-8874081) | curated |
| [Integrin cell surface interactions](https://reactome.org/content/detail/R-HSA-216083) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** protease binding, protein heterodimerization activity.

**Biological process:** regulation of transforming growth factor beta receptor signaling pathway, regulation of Wnt signaling pathway, lung development, regulation of BMP signaling pathway, skin development, mesodermal cell differentiation.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-02-15.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Fulgent Genetics, Fulgent Genetics | Likely pathogenic | criteria provided, single submitter | clinical testing | 2024-02-15 |

## Associated conditions {#conditions}

[epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome](https://sugi.bio/atlas/disease/epidermolysis-bullosa-junctional-7-with-interstitial-lung-disease-and-nephrotic-syndrome/).

**Reported phenotype names (ClinVar):** Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome, Interstitial Lung Disease with Nephrotic Syndrome and Epidermolysis Bullosa, Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital.

## Similar variants {#similar}

Related ITGA3 variant pages (same residue, condition, or type): [ITGA3 c.2401-11_2409del](/variant/itga3-c-2401-minus-11-2409del), [ITGA3 c.2577_2583+13del](/variant/itga3-c-2577-2583-plus-13del), [ITGA3 c.-3_-1del](/variant/itga3-c-minus-3-minus-1del), [ITGA3 p.Pro392fs](/variant/itga3-p-pro392fs), [ITGA3 c.2070+1G>A](/variant/itga3-c-2070-plus-1g-a), [ITGA3 p.Arg274Gln](/variant/itga3-p-arg274gln), [ITGA3 p.Arg875Ter](/variant/itga3-p-arg875ter), [ITGA3 p.Pro81fs](/variant/itga3-p-pro81fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3582280). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*