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: BRCA2 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000059.4(BRCA2):c.7819A>C (p.Thr2607Pro)

CA025298

52422 (ClinVar)

Gene: BRCA2 (HGNC:675)
Condition: BRCA2-related cancer predisposition (MONDO:0700269)
Inheritance Mode: Autosomal dominant inheritance
UUID: 2147d84b-0db5-4482-a760-0b62b024c829
Approved on: 2026-07-15
Published on: 2026-07-15

HGVS expressions

NM_000059.4:c.7819A>C
NM_000059.4(BRCA2):c.7819A>C (p.Thr2607Pro)
NC_000013.11:g.32362536A>C
CM000675.2:g.32362536A>C
NC_000013.10:g.32936673A>C
CM000675.1:g.32936673A>C
NC_000013.9:g.31834673A>C
NG_012772.3:g.52057A>C
ENST00000470094.2:c.7819A>C
ENST00000528762.2:c.7819A>C
ENST00000530893.7:c.7450A>C
ENST00000665585.2:c.7819A>C
ENST00000666593.2:c.7819A>C
ENST00000700202.2:c.7819A>C
ENST00000700202.1:c.286A>C
ENST00000380152.8:c.7819A>C
ENST00000544455.6:c.7819A>C
ENST00000614259.2:c.7827A>C
ENST00000665585.1:c.384A>C
ENST00000680887.1:c.7819A>C
ENST00000380152.7:c.7819A>C
ENST00000544455.5:c.7819A>C
ENST00000614259.1:n.7827A>C
NM_000059.3:c.7819A>C
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Likely Pathogenic

Met criteria codes 3
PS3 PM2_Supporting PP4_Moderate
Not Met criteria codes 4
BP4 BP1 BP7 PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA2 Version 1.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.7819A>C variant in BRCA2 is a missense variant predicted to cause substitution of Threonine by Proline at amino acid 2607 (p.(Thr2607Pro)). This variant is absent from gnomAD v4.1 (read depth ≥25x in >90% samples, PM2_Supporting met). Reported by three calibrated studies to exhibit functional effect similar to pathogenic control variants (PMIDs: 38417439, 39779857, 39779848) and reported by one calibrated study to show an impact of varying degree in different assays (PMID: 32444794) (PS3 met). This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.23, indicating impact on BRCA2 function via protein change is unclear (score range 0.18-0.30). A SpliceAI score of 0.01 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 11.9 (based on Co-occurrence LR=1.03; Family History LR=11.62), within the thresholds for moderate evidence towards pathogenicity (LR >4.3 & ≤18.7) (PP4_Moderate met; Internal lab contributors). In summary, this variant meets the criteria to be classified as a Likely pathogenic variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PP4_Moderate, PS3).
Met criteria codes
PS3
Reported by three calibrated studies to exhibit functional effect similar to pathogenic control variants (PMIDs: 38417439, 39779857, 39779848) and reported by one calibrated study to show an impact of varying degree in different assays (PMID: 32444794) (PS3 met).
PM2_Supporting
This variant is absent from gnomAD v4.1 (read depth ≥25x in >90% samples, PM2_Supporting met).
PP4_Moderate
Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 11.9 (based on Co-occurrence LR=1.03; Family History LR=11.62), within the thresholds for moderate evidence towards pathogenicity (LR >4.3 & ≤18.7) (PP4_Moderate met; Internal lab contributors).
Not Met criteria codes
BP4
This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.23, indicating impact on BRCA2 function via protein change is unclear (score range 0.18-0.30). A SpliceAI score of 0.01 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied).
BP1
This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.23, indicating impact on BRCA2 function via protein change is unclear (score range 0.18-0.30). A SpliceAI score of 0.01 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied).
BP7
This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.23, indicating impact on BRCA2 function via protein change is unclear (score range 0.18-0.30). A SpliceAI score of 0.01 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied).
PP3
This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.23, indicating impact on BRCA2 function via protein change is unclear (score range 0.18-0.30). A SpliceAI score of 0.01 predicts no impact on splicing (score threshold <0.10) (no bioinformatic code is applied).
Curation History
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