NM_018972.4(GDAP1):c.395del (p.Pro132fs) AND Charcot-Marie-Tooth disease type 4A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 13, 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:: RCV003504212.1

Allele description [Variation Report for NM_018972.4(GDAP1):c.395del (p.Pro132fs)]

NM_018972.4(GDAP1):c.395del (p.Pro132fs)

Gene:

GDAP1:ganglioside induced differentiation associated protein 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8q21.11

Genomic location:

Preferred name:

NM_018972.4(GDAP1):c.395del (p.Pro132fs)

HGVS:

NC_000008.11:g.74360221del
NG_008787.3:g.44092del
NM_001040875.4:c.191del
NM_001362929.2:c.68del
NM_001362930.2:c.311-1663del
NM_001362931.2:c.395del
NM_001362932.2:c.68del
NM_018972.4:c.395delMANE SELECT
NP_001035808.1:p.Pro64fs
NP_001349858.1:p.Pro23fs
NP_001349860.1:p.Pro132fs
NP_001349861.1:p.Pro23fs
NP_061845.2:p.Pro132Glnfs
NP_061845.2:p.Pro132fs
LRG_244t1:c.395del
LRG_244:g.44092del
LRG_244p1:p.Pro132Glnfs
NC_000008.10:g.75272455del
NC_000008.10:g.75272456del
NM_018972.2:c.395delC
NR_046346.1:n.329delC

Protein change:

P132fs

Molecular consequence:

NM_001040875.4:c.191del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001362929.2:c.68del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001362931.2:c.395del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001362932.2:c.68del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018972.4:c.395del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001362930.2:c.311-1663del - intron variant - [Sequence Ontology: SO:0001627]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004280287	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11743580, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004280287

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 13, 2023)

germline

clinical testing

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

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

The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease.

Cuesta A, Pedrola L, Sevilla T, García-Planells J, Chumillas MJ, Mayordomo F, LeGuern E, Marín I, Vílchez JJ, Palau F.

Nat Genet. 2002 Jan;30(1):22-5. Epub 2001 Dec 17.

PubMed [citation]

PMID:: 11743580

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 Invitae, SCV004280287.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro132Glnfs*15) in the GDAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GDAP1 are known to be pathogenic (PMID: 11743580). This variant has not been reported in the literature in individuals affected with GDAP1-related conditions. 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: Feb 20, 2024

ClinVar

Relating variation to medicine