rs1060504185
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The NM_058195.4(CDKN2A):c.286C>T(p.Arg96Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/16 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. R96G) has been classified as Likely benign.
Frequency
Consequence
NM_058195.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.286C>T | p.Arg96Cys | missense_variant | 2/3 | ENST00000579755.2 | |
CDKN2A | NM_000077.5 | c.243C>T | p.Pro81= | synonymous_variant | 2/3 | ENST00000304494.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.286C>T | p.Arg96Cys | missense_variant | 2/3 | 1 | NM_058195.4 | ||
CDKN2A | ENST00000304494.10 | c.243C>T | p.Pro81= | synonymous_variant | 2/3 | 1 | NM_000077.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.89e-7 AC: 1AN: 1451858Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 722662
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 23, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 11, 2021 | 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. - |
Familial melanoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 01, 2021 | This sequence change replaces arginine with cysteine at codon 96 of the CDKN2A (p14ARF) protein (p.Arg96Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p14ARF)-related conditions. ClinVar contains an entry for this variant (Variation ID: 532271). 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. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at