The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: BRCA1 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • cspec.ruleSetIri property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec-priv/RuleSet/id/1530970184!
  • cspecId property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec-priv/SequenceVariantInterpretation/id/1530970171!
  • No CSPEC computed assertion could be determined for this classification!

  • No Criteria Specification was provided in the publication event for the variant classifaction.
  • The Criteria Specification shown below is a best-estimate based on the VCEP, gene, disease, and publication date.

Variant: NM_007294.4(BRCA1):c.5202T>G (p.Phe1734Leu)

CA10576081

225711 (ClinVar)

Gene: BRCA1 (HGNC:672)
Condition: BRCA1-related cancer predisposition (MONDO:0700268)
Inheritance Mode: Autosomal dominant inheritance
UUID: f9ff3fc0-3211-4cb4-a369-43bd609c1aa4
Approved on: 2026-01-05
Published on: 2026-01-05

HGVS expressions

NM_007294.4:c.5202T>G
NM_007294.4(BRCA1):c.5202T>G (p.Phe1734Leu)
NC_000017.11:g.43057127A>C
CM000679.2:g.43057127A>C
NC_000017.10:g.41209144A>C
CM000679.1:g.41209144A>C
NC_000017.9:g.38462670A>C
NG_005905.2:g.160857T>G
ENST00000461574.2:c.5199T>G
ENST00000470026.6:c.5202T>G
ENST00000473961.6:c.5076T>G
ENST00000476777.6:c.5196T>G
ENST00000477152.6:c.5124T>G
ENST00000478531.6:c.1890T>G
ENST00000489037.2:c.5124T>G
ENST00000493919.6:c.1752T>G
ENST00000494123.6:c.5202T>G
ENST00000497488.2:c.4314T>G
ENST00000618469.2:c.5202T>G
ENST00000634433.2:c.5079T>G
ENST00000644379.2:c.5268T>G
ENST00000644555.2:c.1752T>G
ENST00000652672.2:c.5061T>G
ENST00000484087.6:c.1764T>G
ENST00000357654.9:c.5202T>G
ENST00000471181.7:c.5265T>G
ENST00000644379.1:c.1589T>G
ENST00000352993.7:c.1776T>G
ENST00000357654.7:c.5202T>G
ENST00000461221.5:c.*4985T>G
ENST00000468300.5:c.1890T>G
ENST00000471181.6:c.5265T>G
ENST00000491747.6:c.1890T>G
ENST00000493795.5:c.5061T>G
ENST00000586385.5:c.132T>G
ENST00000591534.5:c.675T>G
ENST00000591849.5:c.-98-6937T>G
NM_007294.3:c.5202T>G
NM_007297.3:c.5061T>G
NM_007298.3:c.1890T>G
NM_007299.3:c.1890T>G
NM_007300.3:c.5265T>G
NR_027676.1:n.5338T>G
NM_007297.4:c.5061T>G
NM_007299.4:c.1890T>G
NM_007300.4:c.5265T>G
NR_027676.2:n.5379T>G
More

Likely Pathogenic

Met criteria codes 3
PS3 PM2_Supporting PS1_Moderate
Not Met criteria codes 3
BP4 BP1 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.5202T>G variant in BRCA1 is a missense variant predicted to cause substitution of Phenylalanine by Leucine at amino acid 1734 (p.(Phe1734Leu)). This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMID:30209399, 35196514) (PS3 met). This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.27, indicating impact on BRCA1 function via protein change is unclear (score range 0.15-0.28). A SpliceAI score of 0 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied). A different nucleotide change leading to the same amino acid change (c.5200T>C p.Phe1734Leu, ClinVar Variation ID 125806) is classified as likely pathogenic by the ENIGMA BRCA1/2 VCEP. Splicing prediction revealed no effects on splicing due to either variant. These results suggest that the variant has an impact on protein consistent with pathogenicity (PS1_Moderate (Missense) met). In summary, this variant meets the criteria to be classified as a Likely pathogenic Variant for BRCA1-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PS3, PS1_Moderate (Missense)).
Met criteria codes
PS3
Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMID:30209399, 35196514) (PS3 met).
PM2_Supporting
This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met).
PS1_Moderate
A different nucleotide change leading to the same amino acid change (c.5200T>C p.Phe1734Leu, ClinVar Variation ID 125806) is classified as likely pathogenic by the ENIGMA BRCA1/2 VCEP. Splicing prediction revealed no effects on splicing due to either variant. These results suggest that the variant has an impact on protein consistent with pathogenicity (PS1_Moderate (Missense) met).
Not Met criteria codes
BP4
This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.27, indicating impact on BRCA1 function via protein change is unclear (score range 0.15-0.28). A SpliceAI score of 0 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied).
BP1
This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.27, indicating impact on BRCA1 function via protein change is unclear (score range 0.15-0.28). A SpliceAI score of 0 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied).
PP3
This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.27, indicating impact on BRCA1 function via protein change is unclear (score range 0.15-0.28). A SpliceAI score of 0 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
ClinGen Terms of Use.
¤ Powered by BCM's Genboree.