rs6413464
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 4P and 20B. PM1PM5BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000304494.10(CDKN2A):c.379G>T(p.Ala127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,610,798 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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. A127P) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000304494.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.379G>T | p.Ala127Ser | missense_variant | 2/3 | ENST00000304494.10 | NP_000068.1 | |
CDKN2A | NM_058195.4 | c.*23G>T | 3_prime_UTR_variant | 2/3 | ENST00000579755.2 | NP_478102.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.379G>T | p.Ala127Ser | missense_variant | 2/3 | 1 | NM_000077.5 | ENSP00000307101 | P2 | |
CDKN2A | ENST00000579755.2 | c.*23G>T | 3_prime_UTR_variant | 2/3 | 1 | NM_058195.4 | ENSP00000462950 |
Frequencies
GnomAD3 genomes AF: 0.00487 AC: 741AN: 152236Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00129 AC: 316AN: 244500Hom.: 0 AF XY: 0.000991 AC XY: 132AN XY: 133184
GnomAD4 exome AF: 0.000541 AC: 789AN: 1458444Hom.: 7 Cov.: 31 AF XY: 0.000445 AC XY: 323AN XY: 725684
GnomAD4 genome AF: 0.00488 AC: 743AN: 152354Hom.: 6 Cov.: 32 AF XY: 0.00444 AC XY: 331AN XY: 74506
ClinVar
Submissions by phenotype
not provided Benign:5
Benign, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 06, 2018 | This variant is associated with the following publications: (PMID: 26650189, 28944238, 18983535, 25780468, 7970734, 26104880, 22703879, 22995991, 25064638, 15860862, 20981092, 24728327, 9823374, 19141585, 26775776, 7777061, 10498896, 21462282, 12485439, 29552713, 20505745, 18573309) - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 15, 2022 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 22, 2023 | - - |
not specified Benign:4Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 01, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 30, 2017 | - - |
Hereditary cancer-predisposing syndrome Benign:4
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 26, 2020 | - - |
Benign, no assertion criteria provided | clinical testing | True Health Diagnostics | Oct 10, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 26, 2014 | This alteration is classified as 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. - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 23, 2016 | - - |
Melanoma-pancreatic cancer syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Counsyl | Jul 12, 2016 | - - |
Melanoma and neural system tumor syndrome;C1835044:Melanoma, cutaneous malignant, susceptibility to, 2;C1838547:Melanoma-pancreatic cancer syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 15, 2022 | - - |
Familial melanoma Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at