rs376868259
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018972.4(GDAP1):โc.5C>Gโ(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000741 in 1,605,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (โ โ ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2T) has been classified as Uncertain significance.
Frequency
Consequence
NM_018972.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDAP1 | NM_018972.4 | c.5C>G | p.Ala2Gly | missense_variant | 1/6 | ENST00000220822.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDAP1 | ENST00000220822.12 | c.5C>G | p.Ala2Gly | missense_variant | 1/6 | 1 | NM_018972.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152264Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000153 AC: 38AN: 249130Hom.: 0 AF XY: 0.000230 AC XY: 31AN XY: 134910
GnomAD4 exome AF: 0.0000791 AC: 115AN: 1453090Hom.: 1 Cov.: 30 AF XY: 0.000122 AC XY: 88AN XY: 723468
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152264Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74388
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 09, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variantยฌโ is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 467766). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). This variant is present in population databases (rs376868259, gnomAD 0.1%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 2 of the GDAP1 protein (p.Ala2Gly). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 18, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at