rs947790209
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBP6
The ENST00000304494.10(CDKN2A):c.7C>T(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,591,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3L) has been classified as Likely benign.
Frequency
Consequence
ENST00000304494.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.7C>T | p.Pro3Ser | missense_variant | 1/3 | ENST00000304494.10 | NP_000068.1 | |
CDKN2A | NM_058195.4 | c.194-3613C>T | intron_variant | ENST00000579755.2 | NP_478102.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.7C>T | p.Pro3Ser | missense_variant | 1/3 | 1 | NM_000077.5 | ENSP00000307101 | P2 | |
CDKN2A | ENST00000579755.2 | c.194-3613C>T | intron_variant | 1 | NM_058195.4 | ENSP00000462950 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000466 AC: 1AN: 214480Hom.: 0 AF XY: 0.00000840 AC XY: 1AN XY: 119068
GnomAD4 exome AF: 0.00000139 AC: 2AN: 1439510Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1AN XY: 715510
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74270
ClinVar
Submissions by phenotype
Familial melanoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2021 | This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. This sequence change replaces proline with serine at codon 3 of the CDKN2A (p16INK4a) protein (p.Pro3Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at