The BRCA2 c.831T>G (p.Asn277Lys) variant has been reported in ClinVar and is classified as Benign by the ClinGen ENIGMA BRCA1/2 expert panel.1 This variant is present in population databases, including gnomAD v2.1 at AF 0.0000687 with a highest observed filter allele frequency of 0.0001033 and gnomAD v4.1 at AF 0.0001886 with a highest observed filter allele frequency of 0.0002296, supporting BS1.2 Calibrated functional data in the ENIGMA BRCA1/2 specification support no damaging effect on protein function for p.(Asn277Lys), supporting BS3.3 In silico evidence does not suggest splice disruption, with a SpliceAI maximum delta score of 0.00, and the missense change lies outside the BRCA2 clinically important domains used by ENIGMA for missense interpretation, supporting BP1_Strong.4
BRCA2
Final classification
Benign
BRCA2 c.831T>G · p.Asn277Lys
BRCA2
The BRCA2 c.831T>G (p.Asn277Lys) variant has been reported in ClinVar and is classified as Benign by the ClinGen ENIGMA BRCA1/2 expert panel.
Official ClinGen/ENIGMA BRCA1/2 final-classification framework used: ENIGMA BRCA1 and BRCA2 Specification v1.2, Table 3 criteria-combination rules via the final_classification_framework override.
Classification rationale
BS1BS3BP1BP6
Benign
BRCA2 c.831T>G
BS1 + BS3 + BP1 + BP6
→
Benign
3
vcep_specifications_table9_v1_2_2024_11_18cspec ↗
Gene diagram
· NM_000059.4 · variants mapped to exon structure
BRCA2
NM_000059.4
Fetching transcript structure from UCSC…
Applied criteria · 4 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency · supports benign
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 0.000188639; MAF= 0.01886%, 303/1606240 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000253241; MAF= 0.02532%, 298/1176744 alleles, homozygotes = 0); grpmax FAF= 0.0002296.
v2.1
This variant is present in gnomAD v2.1 (AF= 6.87096e-05; MAF= 0.00687%, 19/276526 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000149258; MAF= 0.01493%, 19/127296 alleles, homozygotes = 0); grpmax FAF= 0.0001033.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.019%
· 303 / 1,606,240
0 hom · FAF 0.023%
0 hom · FAF 0.023%
European (non-Finnish) 298 / 1,176,744 |
0.025% |
Remaining individuals 4 / 62,198 |
0.0064% |
African/African American 1 / 74,526 |
0.0013% |
+ 7 not observed (Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish)
gnomAD v2.1
0.0069%
· 19 / 276,526
0 hom · FAF 0.01%
0 hom · FAF 0.01%
European (non-Finnish) 19 / 127,296 |
0.015% |
+ 7 not observed (African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian)
ClinVar
This variant has been reported in ClinVar as Likely benign (13 clinical laboratories) and as Benign (5 clinical laboratories) and as Uncertain significance (5 clinical laboratories) and as likely benign (1 clinical laboratory) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
Unknown Oncogenic Effect
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: BRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Hotspots
This variant does not lie in a statistically significant hotspot.
Literature · how each cited paper was used
1papers cited
Each card is an audit: what was searched, what was found, whether it names the variant, which criteria it fed, and why.
PMID PMID:33293522
Found
Structured finding pending for this record — see source link.
Applied to
→BS3 supports · met
Sources & reference links