rs587778191
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BP6
The NM_058195.4(CDKN2A):c.340G>T(p.Gly114Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 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. G114V) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.340G>T | p.Gly114Cys | missense_variant | 2/3 | ENST00000579755.2 | |
CDKN2A | NM_000077.5 | c.297G>T | p.Arg99= | synonymous_variant | 2/3 | ENST00000304494.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.340G>T | p.Gly114Cys | missense_variant | 2/3 | 1 | NM_058195.4 | ||
CDKN2A | ENST00000304494.10 | c.297G>T | p.Arg99= | synonymous_variant | 2/3 | 1 | NM_000077.5 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1453124Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 723192
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 16, 2019 | The c.297G>T variant (also known as p.R99R), located in coding exon 2, results from a G to T substitution at nucleotide position 297 of the p16 protein-encoding isoform of the CDKN2A gene. This nucleotide substitution does not change the amino acid at codon 99 in the p16 reading frame. This alteration also results in the p.G114C variant (also known as c.340G>T) of the p14 protein-encoding isoform of the CDKN2A gene. The glycine at codon 114 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Familial melanoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2020 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at