NM_018972.4(GDAP1):c.839A>C (p.Tyr280Ser) AND Charcot-Marie-Tooth disease type 4A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 21, 2023
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:: RCV000818644.9

Allele description [Variation Report for NM_018972.4(GDAP1):c.839A>C (p.Tyr280Ser)]

NM_018972.4(GDAP1):c.839A>C (p.Tyr280Ser)

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.839A>C (p.Tyr280Ser)

HGVS:

NC_000008.11:g.74364129A>C
NG_008787.3:g.48000A>C
NM_001040875.4:c.635A>C
NM_001362929.2:c.512A>C
NM_001362930.2:c.665A>C
NM_001362931.2:c.694+1076A>C
NM_001362932.2:c.512A>C
NM_018972.4:c.839A>CMANE SELECT
NP_001035808.1:p.Tyr212Ser
NP_001349858.1:p.Tyr171Ser
NP_001349859.1:p.Tyr222Ser
NP_001349861.1:p.Tyr171Ser
NP_061845.2:p.Tyr280Ser
LRG_244t1:c.839A>C
LRG_244:g.48000A>C
NC_000008.10:g.75276364A>C
NM_018972.2:c.839A>C

Protein change:

Y171S

Links:

dbSNP: rs1417699318

NCBI 1000 Genomes Browser:

rs1417699318

Molecular consequence:

NM_001362931.2:c.694+1076A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001040875.4:c.635A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001362929.2:c.512A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001362930.2:c.665A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001362932.2:c.512A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_018972.4:c.839A>C - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000959268	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 21, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000959268

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 21, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000959268.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 280 of the GDAP1 protein (p.Tyr280Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal recessive Charcot-Marie-Tooth disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 661259). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine