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LYFE SCIENCES
Project: HERA
NM_000059.4:c.7976+24G>A
p.?  ·  BRCA2
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Classification rationale
1

The BRCA2 NM_000059.4:c.7976+24G>A (NP_000050.3:p.?) variant has been reported in ClinVar (Variation ID 371868), although submission-level classification details were not available in the reviewed record.

clinvar ↗
2

This variant is present in population databases, including gnomAD v2.1 at 12/250842 alleles with an East Asian grpmax filter allele frequency of 0.00037674 and gnomAD v4.1 at 94/1612498 alleles; the gnomAD v2.1 frequency exceeds the ENIGMA BRCA2 BS1 strong threshold of 0.0001.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

In silico splicing prediction does not support an abnormal splicing effect, with a SpliceAI maximum delta score of 0.00, consistent with BP4 and BP7 and arguing against PP3.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 4.78389e-05; MAF= 0.00478%, 12/250842 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000653239; MAF= 0.06532%, 12/18370 alleles, homozygotes = 0); grpmax FAF= 0.00037674.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 5.82946e-05; MAF= 0.00583%, 94/1612498 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.0018502; MAF= 0.18502%, 83/44860 alleles, homozygotes = 0); grpmax FAF= 0.00152896.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant is present in ClinVar (Variation ID: 371868); submission details unavailable.
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.