Classification rationale

BA1BS1BP4BP7 Benign

BRCA2 c.682-30A>C

The BRCA2 c.682-30A>C (p.?) variant has been reported in ClinVar as benign by 2 clinical laboratories and likely benign by 2 clinical laboratories.¹ This variant is present in gnomAD with a group maximum filter allele frequency of 0.00539635 in v2.1 and 0.00494792 in v4.1, both above the ENIGMA BRCA2 BA1 threshold of 0.001 and the BS1 strong threshold of 0.0001.² SpliceAI predicts no significant splice impact for this intronic variant, with a maximum delta score of 0.01, which supports BP4 and BP7 under the ENIGMA BRCA2 splicing rules.³

BA1 + BS1 + BP4 + BP7 → Benign

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗cspec ↗

3 spliceai ↗cspec ↗

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= 0.000289734; MAF= 0.02897%, 391/1349516 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.00539895; MAF= 0.53989%, 375/69458 alleles, homozygotes = 1); grpmax FAF= 0.00494792.

v2.1

This variant is present in gnomAD v2.1 (AF= 0.000536223; MAF= 0.05362%, 136/253626 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.0060639; MAF= 0.60639%, 134/22098 alleles, homozygotes = 1); grpmax FAF= 0.00539635.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.029% · 391 / 1,349,516
1 hom · FAF 0.49%

African/African American 375 / 69,458	0.54% 1 hom
Remaining individuals 10 / 53,468	0.019%
Admixed American 5 / 57,824	0.0086%
European (non-Finnish) 1 / 945,462	0.00011%

+ 6 not observed (European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish)

gnomAD v2.1

0.054% · 136 / 253,626
1 hom · FAF 0.54%

African/African American 134 / 22,098	0.61% 1 hom
Admixed American 2 / 33,220	0.006%

+ 6 not observed (Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian)

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant has been reported in ClinVar as Benign (2 clinical laboratories) and as Likely benign (2 clinical laboratories).

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Literature · how each cited paper was used

4papers 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

PMID cspec ↗

Found

Structured finding pending for this record — see source link.

Applied to

→BA1 supports · met →BP4 supports · met →BP7 supports · met →BS1 supports · met

PMID gnomad_v2

PMID gnomad_v2 ↗

Found

Structured finding pending for this record — see source link.

Applied to

→BA1 supports · met →BS1 supports · met

PMID gnomad_v4

PMID gnomad_v4 ↗

Found

Structured finding pending for this record — see source link.

Applied to

→BA1 supports · met →BS1 supports · met

PMID spliceai

PMID spliceai ↗

Found

Structured finding pending for this record — see source link.

Applied to

→BP4 supports · met →BP7 supports · met

Sources & reference links

7Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC