9-21971062-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong
The NM_058195.4(CDKN2A):c.340G>A(p.Gly114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G114C) has been classified as Likely benign.
Frequency
Consequence
NM_058195.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.340G>A | p.Gly114Ser | missense_variant | Exon 2 of 3 | 1 | NM_058195.4 | ENSP00000462950.1 | ||
CDKN2A | ENST00000304494.10 | c.297G>A | p.Arg99Arg | synonymous_variant | Exon 2 of 3 | 1 | NM_000077.5 | ENSP00000307101.5 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 152212Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.00000426 AC: 1AN: 234492Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128946
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1453124Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 723192
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
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. -
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Familial melanoma Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at