rs878855054
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate
The NM_018972.4(GDAP1):āc.614T>Cā(p.Leu205Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,583,892 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L205W) has been classified as Likely pathogenic.
Frequency
Consequence
NM_018972.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GDAP1 | NM_018972.4 | c.614T>C | p.Leu205Ser | missense_variant | 5/6 | ENST00000220822.12 | NP_061845.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GDAP1 | ENST00000220822.12 | c.614T>C | p.Leu205Ser | missense_variant | 5/6 | 1 | NM_018972.4 | ENSP00000220822.7 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152070Hom.: 0 Cov.: 29
GnomAD4 exome AF: 0.0000140 AC: 20AN: 1431822Hom.: 0 Cov.: 27 AF XY: 0.0000182 AC XY: 13AN XY: 714472
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152070Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1AN XY: 74282
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2016 | In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a GDAP1-related disease. This sequence change replaces leucine with serine at codon 205 of the GDAP1 protein (p.Leu205Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at