rs1060504184
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000077.5(CDKN2A):c.81G>T(p.Glu27Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000077.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDKN2A | NM_000077.5 | c.81G>T | p.Glu27Asp | missense_variant | 1/3 | ENST00000304494.10 | NP_000068.1 | |
CDKN2A | NM_058195.4 | c.194-3539G>T | intron_variant | ENST00000579755.2 | NP_478102.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDKN2A | ENST00000304494.10 | c.81G>T | p.Glu27Asp | missense_variant | 1/3 | 1 | NM_000077.5 | ENSP00000307101.5 | ||
CDKN2A | ENST00000579755.2 | c.194-3539G>T | intron_variant | 1 | NM_058195.4 | ENSP00000462950.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151976Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151976Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74218
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 07, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Familial melanoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 06, 2019 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDKN2A (p16INK4a)-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 27 of the CDKN2A (p16INK4a) protein (p.Glu27Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at