rs34968276
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PVS1PM2BP6
The NM_058195.4(CDKN2A):c.292C>T(p.Arg98Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000138 in 1,452,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R98R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_058195.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN2A | NM_058195.4 | c.292C>T | p.Arg98Ter | stop_gained | 2/3 | ENST00000579755.2 | |
CDKN2A | NM_000077.5 | c.249C>T | p.His83= | synonymous_variant | 2/3 | ENST00000304494.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000579755.2 | c.292C>T | p.Arg98Ter | stop_gained | 2/3 | 1 | NM_058195.4 | ||
CDKN2A | ENST00000304494.10 | c.249C>T | p.His83= | synonymous_variant | 2/3 | 1 | NM_000077.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1452118Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 722772
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2019 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 24, 2018 | - - |
Familial melanoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 16, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at