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NM_018972.4(GDAP1):c.714G>A (p.Trp238Ter) AND Charcot-Marie-Tooth disease type 4A

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Aug 23, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002610213.4

Allele description [Variation Report for NM_018972.4(GDAP1):c.714G>A (p.Trp238Ter)]

NM_018972.4(GDAP1):c.714G>A (p.Trp238Ter)

Gene:
GDAP1:ganglioside induced differentiation associated protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.11
Genomic location:
Preferred name:
NM_018972.4(GDAP1):c.714G>A (p.Trp238Ter)
HGVS:
  • NC_000008.11:g.74364004G>A
  • NG_008787.3:g.47875G>A
  • NM_001040875.4:c.510G>A
  • NM_001362929.2:c.387G>A
  • NM_001362930.2:c.540G>A
  • NM_001362931.2:c.694+951G>A
  • NM_001362932.2:c.387G>A
  • NM_018972.4:c.714G>AMANE SELECT
  • NP_001035808.1:p.Trp170Ter
  • NP_001349858.1:p.Trp129Ter
  • NP_001349859.1:p.Trp180Ter
  • NP_001349861.1:p.Trp129Ter
  • NP_061845.2:p.Trp238Ter
  • NP_061845.2:p.Trp238Ter
  • LRG_244t1:c.714G>A
  • LRG_244:g.47875G>A
  • LRG_244p1:p.Trp238Ter
  • NC_000008.10:g.75276239G>A
  • NM_018972.2:c.714G>A
  • NR_046346.1:n.648G>A
Protein change:
W129*
Molecular consequence:
  • NM_001362931.2:c.694+951G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001040875.4:c.510G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001362929.2:c.387G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001362930.2:c.540G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001362932.2:c.387G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_018972.4:c.714G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Charcot-Marie-Tooth disease type 4A
Synonyms:
Charcot-Marie-Tooth disease, demyelinating, autosomal recessive; Charcot-Marie-Tooth disease, demyelinating, autosomal recessive, type 4a; Charcot-Marie-Tooth Neuropathy Type 4A
Identifiers:
MONDO: MONDO:0008961; MedGen: C1859198; Orphanet: 99948; OMIM: 214400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003493469Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 23, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004174597Inherited Neuropathy Consortium Ii, University Of Miami
no assertion criteria provided
Uncertain significance
(May 8, 2017) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedliterature only
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

The allelic spectrum of Charcot-Marie-Tooth disease in over 17,000 individuals with neuropathy.

DiVincenzo C, Elzinga CD, Medeiros AC, Karbassi I, Jones JR, Evans MC, Braastad CD, Bishop CM, Jaremko M, Wang Z, Liaquat K, Hoffman CA, York MD, Batish SD, Lupski JR, Higgins JJ.

Mol Genet Genomic Med. 2014 Nov;2(6):522-9. doi: 10.1002/mgg3.106. Epub 2014 Aug 21.

PubMed [citation]
PMID:
25614874
PMCID:
PMC4303222

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003493469.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Trp238*) in the GDAP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 121 amino acid(s) of the GDAP1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 25614874). This variant disrupts a region of the GDAP1 protein in which other variant(s) (p.Arg341Glnfs*12) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Inherited Neuropathy Consortium Ii, University Of Miami, SCV004174597.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024