BLM c.2074+2T>C
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Bloom syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.74 | donor loss · deltas |
| Pangolin | Δ0.80 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2.6, phastCons 1 |
| Non-coding constraint | Z 2.34 | 1 kb window · o/e 0.83 · regional · uncalibrated |
| Overall | ||
| CADD | 28.4 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- BLM
- Coding
- c.2074+2T>C
- MANE Select
- NM_000057
- Type
- single nucleotide variant
- Location
- chr15:90763159 (GRCh38)
- Gene constraint
- LOEUF 0.847 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 61.10 · 16 PDB
Disease context
Bloom syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Bloom syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Antenatal, Neonatal
- Prevalence
- 1-9 / 100 000 (Specific population)
Similar variants
- BLM c.1087+1G>A Likely pathogenic ★★ same condition
- BLM c.1088-1G>A Likely pathogenic ★★ same condition
- BLM c.1220+2T>C Likely pathogenic ★★ same condition
- BLM c.1220+2T>G Likely pathogenic ★★ same condition
- BLM c.1882+2T>C Likely pathogenic ★★ same condition
- BLM c.2074+1G>T Likely pathogenic ★★ same condition
- BLM c.2075-1G>A Likely pathogenic ★★ same condition
- BLM c.2193+1G>A Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/blm-c-2074-plus-2t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown