9-21974696-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000077.5(CDKN2A):c.132C>A(p.Tyr44Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y44Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000077.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.132C>A | p.Tyr44Ter | stop_gained | 1/3 | ENST00000304494.10 | |
CDKN2A | NM_058195.4 | c.194-3488C>A | intron_variant | ENST00000579755.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.132C>A | p.Tyr44Ter | stop_gained | 1/3 | 1 | NM_000077.5 | P2 | |
CDKN2A | ENST00000579755.2 | c.194-3488C>A | intron_variant | 1 | NM_058195.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial melanoma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2018 | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in an individual and a family affected with melanoma (PMID: 9699728, 16234564). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr44*) in the CDKN2A (p16INK4a) gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDKN2A (p16INK4a) are known to be pathogenic (PMID: 15146471, 16905682). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at