Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_018972.4(GDAP1):c.965C>T(p.Thr322Met) variant causes a missense change. The variant allele was found at a frequency of 0.000177 in 1,614,016 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T322A) has been classified as Uncertain significance.
GDAP1 (HGNC:15968): (ganglioside induced differentiation associated protein 1) This gene encodes a member of the ganglioside-induced differentiation-associated protein family, which may play a role in a signal transduction pathway during neuronal development. Mutations in this gene have been associated with various forms of Charcot-Marie-Tooth Disease and neuropathy. Two transcript variants encoding different isoforms and a noncoding variant have been identified for this gene. [provided by RefSeq, Feb 2012]
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
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PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
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BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.044024974).
BP6
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BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-74364255-C-T is Benign according to our data. Variant chr8-74364255-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 467776.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=4, Likely_benign=3}.
Likely benign, criteria provided, single submitter
clinical testing
GeneDx
Mar 11, 2021
This variant is associated with the following publications: (PMID: 25614874) -
Uncertain significance, criteria provided, single submitter
clinical testing
Revvity Omics, Revvity
Nov 25, 2021
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Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter
clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre
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Charcot-Marie-Tooth disease recessive intermediate A Uncertain:1
Uncertain significance, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Apr 27, 2017
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter
clinical testing
Illumina Laboratory Services, Illumina
Apr 27, 2017
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter
clinical testing
Ambry Genetics
Apr 27, 2022
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. -
Charcot-Marie-Tooth disease type 4A Benign:1
Likely benign, criteria provided, single submitter