chr9-21971044-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM1BP4_StrongBP6BS2
The NM_058195.4(CDKN2A):c.358C>T(p.Arg120Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,453,282 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/15 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. R120S) has been classified as Uncertain significance.
Frequency
Consequence
NM_058195.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.358C>T | p.Arg120Cys | missense_variant | 2/3 | ENST00000579755.2 | |
CDKN2A | NM_000077.5 | c.315C>T | p.Asp105= | synonymous_variant | 2/3 | ENST00000304494.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.358C>T | p.Arg120Cys | missense_variant | 2/3 | 1 | NM_058195.4 | ||
CDKN2A | ENST00000304494.10 | c.315C>T | p.Asp105= | synonymous_variant | 2/3 | 1 | NM_000077.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000851 AC: 2AN: 234900Hom.: 0 AF XY: 0.00000775 AC XY: 1AN XY: 129008
GnomAD4 exome AF: 0.00000619 AC: 9AN: 1453282Hom.: 1 Cov.: 31 AF XY: 0.00000830 AC XY: 6AN XY: 723252
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial melanoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 16, 2021 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2019 | In silico models in agreement (benign);Other strong data supporting benign classification - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at