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LYFE SCIENCES
Project: HERA
NM_000059.3:c.68-7del
p.?  ·  BRCA2
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Classification rationale
1

The BRCA2 c.68-7del (p.?) variant has been reported in ClinVar and is classified as Benign by the ClinGen ENIGMA BRCA1 and BRCA2 expert panel, although some ClinVar submissions remain uncertain significance.

clinvar ↗
2

This variant is present in gnomAD, and in gnomAD v2.1 the grpmax filter allele frequency is 0.00155833, which is above the ENIGMA BRCA2 BA1 threshold of 0.001 and the BS1 strong threshold of 0.0001.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

Computational splicing evidence does not support a deleterious effect because SpliceAI predicts a maximum delta score of 0.04, which is below the BRCA2 BP4 threshold of 0.1 and below the PP3 threshold of 0.2.

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= 0.000846545; MAF= 0.08465%, 198/233892 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.00201734; MAF= 0.20173%, 47/23298 alleles, homozygotes = 0); grpmax FAF= 0.00155833.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.000261677; MAF= 0.02617%, 409/1562996 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 0.000730943; MAF= 0.07309%, 42/57460 alleles, homozygotes = 0); grpmax FAF= 0.00055521.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (5 clinical laboratories) and as Uncertain significance (3 clinical laboratories) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 52188)
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 = 0.04).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV66448762, n = 8 times).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.