Starting

Initialising…

CDKN2A

Final classification

VUS

CDKN2A c.183G>A · p.Glu61=

CDKN2A

The CDKN2A c.183G>A (p.Glu61=) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.

Gene

CDKN2A

Transcript

NM_000077.5

HGVS · transcript:coding

NM_000077.5:c.183G>A

Consequence

N/A

GRCh38

chr9:21971176 C>T

GRCh37

chr9:21971175 C>T

Basis Generic ACMG/AMP 2015 final-classification combination rules were used as the applicable fallback framework because no usable official VCEP/CSPEC or local custom gene-specific final-classification framework was present. ▾

Generic ACMG/AMP 2015 final-classification combination rules were used as the applicable fallback framework because no usable official VCEP/CSPEC or local custom gene-specific final-classification framework was present.

Classification rationale

PM2 BP7 VUS

CDKN2A c.183G>A

The CDKN2A c.183G>A (p.Glu61=) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and observed at 0/1,596,036 alleles in gnomAD v4.1 (AF 0.00000%), which is below the 0.1% PM2 rarity threshold.² In silico data support a silent variant without splice effect: the protein consequence is p.(Glu61=), SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and REVEL is 0.083.³

PM2 + BP7 → VUS

1 cosmic ↗clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗prefetch

Gene diagram · NM_000077.5 · variants mapped to exon structure

CDKN2A NM_000077.5

Fetching transcript structure from UCSC…

Applied criteria · 2 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1596036 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/74908 alleles, homozygotes = 0).

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / 1,596,036
0 hom

Not observed in any ancestry group.

+ 10 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish))

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant hotspot.

COSMIC ↗ Hotspots ↗

Sources & reference links

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots