The BRCA2 c.9234C>T (p.Val3078=; p.V3078=) variant has been reported in ClinVar and is classified as Benign by the ClinGen ENIGMA BRCA1/BRCA2 expert panel.1 This variant is present at low frequency in gnomAD, with AF 1.77e-05 in v2.1 and AF 2.11e-05 in v4.1; these frequencies are above the ENIGMA PM2 absence-from-controls requirement and below the BS1 and BA1 frequency thresholds.2 In the BRCA2 clinical-history likelihood-ratio dataset, this variant has an LR of 0.284 from 12 probands, which is in the benign direction and meets ENIGMA BP5 at Supporting strength.3 Computational splice prediction does not support splice disruption: SpliceAI shows a maximum delta score of 0.06, below the ENIGMA BP4/BP7 threshold of 0.1 and below the PP3 splice threshold of 0.2.4
BRCA2
Final classification
Likely Benign
BRCA2 c.9234C>T · p.Val3078=
BRCA2
The BRCA2 c.9234C>T (p.Val3078=; p.V3078=) variant has been reported in ClinVar and is classified as Benign by the ClinGen ENIGMA BRCA1/BRCA2 expert panel.
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework
Classification rationale
BP4BP5BP6BP7
Likely Benign
BRCA2 c.9234C>T
BP4 + BP5 + BP6 + BP7
→
Likely Benign
3
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗cspec ↗
Gene diagram
· NM_000059.3 · variants mapped to exon structure
BRCA2
NM_000059.3
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= 2.10731e-05; MAF= 0.00211%, 34/1613428 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.71218e-05; MAF= 0.00271%, 32/1179862 alleles, homozygotes = 0); grpmax FAF= 1.963e-05.
v2.1
This variant is present in gnomAD v2.1 (AF= 1.77165e-05; MAF= 0.00177%, 5/282222 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.10212e-05; MAF= 0.00310%, 4/128944 alleles, homozygotes = 0); grpmax FAF= 7.02e-06.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.0021%
· 34 / 1,613,428
0 hom · FAF 0.002%
0 hom · FAF 0.002%
European (non-Finnish) 32 / 1,179,862 |
0.0027% |
Admixed American 1 / 59,902 |
0.0017% |
Remaining individuals 1 / 62,458 |
0.0016% |
+ 7 not observed (European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American)
gnomAD v2.1
0.0018%
· 5 / 282,222
0 hom · FAF 0.0007%
0 hom · FAF 0.0007%
European (non-Finnish) 4 / 128,944 |
0.0031% |
Admixed American 1 / 35,282 |
0.0028% |
+ 6 not observed (African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian)
ClinVar
This variant has been reported in ClinVar as Likely benign (9 clinical laboratories) and as Benign (2 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Uncertain significance (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 = 0.06).
Functional
Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV107498217, n = 1 times).
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:31853058
Found
Structured finding pending for this record — see source link.
Applied to
→BP5 supports · met
Sources & reference links