Classification rationale
No rationale recorded.
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
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
- —
Gaps remaining
- —
Rule
—
Publications
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Research and evidence
v2.1
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 3.97741e-06; MAF= 0.00040%, 1/251420 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79306e-06; MAF= 0.00088%, 1/113726 alleles, homozygotes = 0).
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 3.10151e-06; MAF= 0.00031%, 5/1612120 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.24356e-06; MAF= 0.00042%, 5/1178256 alleles, homozygotes = 0); grpmax FAF= 1.24e-06.
02
ClinVar
This variant has been reported in ClinVar as Pathogenic (22 clinical laboratories) and as pathogenic (1 clinical laboratory) and as Pathogenic by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 128144)
03
Functional
OncoKB: Likely Oncogenic
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
05
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV104552896, n = 1 times).
06
Cancer hotspots
Not found
This variant does not lie in a statistically significant hotspot.