Evidence Repository
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.6859A>T (p.Arg2287Ter)

CA387792666

575178 (ClinVar)

Gene: BRCA2
Condition: BRCA2-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3364ff23-c57d-4025-9a7d-f69cf58a4ac4
Approved on: 2025-05-23
Published on: 2025-05-23

HGVS expressions

NM_000059.4:c.6859A>T
NM_000059.4(BRCA2):c.6859A>T (p.Arg2287Ter)
NC_000013.11:g.32344575A>T
CM000675.2:g.32344575A>T
NC_000013.10:g.32918712A>T
CM000675.1:g.32918712A>T
NC_000013.9:g.31816712A>T
NG_012772.3:g.34096A>T
ENST00000470094.2:c.6859A>T
ENST00000528762.2:c.6859A>T
ENST00000530893.7:c.6490A>T
ENST00000665585.2:c.6859A>T
ENST00000666593.2:c.6859A>T
ENST00000700202.2:c.6859A>T
ENST00000380152.8:c.6859A>T
ENST00000544455.6:c.6859A>T
ENST00000614259.2:c.6859A>T
ENST00000680887.1:c.6859A>T
ENST00000380152.7:c.6859A>T
ENST00000544455.5:c.6859A>T
ENST00000614259.1:n.6859A>T
NM_000059.3:c.6859A>T
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Pathogenic

Met criteria codes 2
PS3 PVS1
Not Met criteria codes 2
PM5 PM2

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 1.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.6859A>T variant in BRCA2 is predicted to cause a change in the length of the protein due to the insertion of a terminating codon instead of the usual arginine at amino acid 2287 (p.(Arg2287Ter)). This variant is present in gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met). Nonsense of exon 12 variant predicted to cause a premature stop codon in biologically-relevant-exon 12/27 leading to nonsense mediated decay (PVS1 met). Reported by one calibrated study to exhibit protein function similar to pathogenic control variants (PMID:32046981) (PS3 met). In summary, this variant meets the criteria to be classified as a Pathogenic variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PVS1, PS3).
Met criteria codes
PS3
Reported by one calibrated study to exhibit protein function similar to pathogenic control variants (PMID:32046981) (PS3 met).
PVS1
Nonsense of exon 12 variant predicted to cause a premature stop codon in biologically-relevant-exon 12/27 leading to nonsense mediated decay (PVS1 met).
Not Met criteria codes
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
This variant is present in gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met).
Curation History
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