The BRCA2 NM_000059.4:c.2820A>G (p.(Gln940=), p.(Q940=)) variant has been reported in ClinVar as likely benign, including review by the ENIGMA expert panel and multiple clinical laboratories.1 This variant is present at very low frequency in population databases, with 1/250640 alleles in gnomAD v2.1 (AF 0.00040%) and 1/1613806 alleles in gnomAD v4.1 (AF 0.00006%), which does not meet ENIGMA benign stand-alone or strong population thresholds and does not satisfy PM2 absence criteria.2 In silico splicing analysis predicts no significant splice impact, with a SpliceAI maximum delta score of 0.00, and the synonymous p.(Gln940=) change lies outside the BRCA2 clinically important domains defined by ENIGMA, supporting BP1_Strong and arguing against PP3.3
BRCA2
Final classification
Likely benign
BRCA2 c.2820A>G · p.Gln940=
BRCA2
The BRCA2 NM_000059.4:c.2820A>G (p.(Gln940=), p.(Q940=)) variant has been reported in ClinVar as likely benign, including review by the ENIGMA expert panel and multiple clinical laboratories.
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework (official CSPEC/VCEP criteria-combination rules).
Classification rationale
BP1BP6
Likely benign
BRCA2 c.2820A>G
BP1 + BP6
→
Likely benign
Gene diagram
· NM_000059.4 · variants mapped to exon structure
BRCA2
NM_000059.4
Fetching transcript structure from UCSC…
Applied criteria · 2 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= 6.19653e-07; MAF= 0.00006%, 1/1613806 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23065e-05; MAF= 0.00223%, 1/44830 alleles, homozygotes = 0).
v2.1
This variant is present in gnomAD v2.1 (AF= 3.98979e-06; MAF= 0.00040%, 1/250640 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.43833e-05; MAF= 0.00544%, 1/18388 alleles, homozygotes = 0).
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
6.2e-05%
· 1 / 1,613,806
0 hom
0 hom
East Asian 1 / 44,830 |
0.0022% |
+ 9 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish))
gnomAD v2.1
0.0004%
· 1 / 250,640
0 hom
0 hom
East Asian 1 / 18,388 |
0.0054% |
+ 7 not observed (African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian)
ClinVar
This variant has been reported in ClinVar as Likely benign (6 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Likely benign by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
Unknown Oncogenic Effect
OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).
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 cspec
Found
Structured finding pending for this record — see source link.
Applied to
→BP1 supports · met
→BP6 supports · met
Sources & reference links