NM_016156.6(MTMR2):c.1537_1538dup (p.Ser514fs) AND Charcot-Marie-Tooth disease type 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 5, 2020
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:: RCV000465990.5

Allele description [Variation Report for NM_016156.6(MTMR2):c.1537_1538dup (p.Ser514fs)]

NM_016156.6(MTMR2):c.1537_1538dup (p.Ser514fs)

Gene:

MTMR2:myotubularin related protein 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11q21

Genomic location:

Preferred name:

NM_016156.6(MTMR2):c.1537_1538dup (p.Ser514fs)

HGVS:

NC_000011.10:g.95838149TA[3]
NG_008333.1:g.91056TA[3]
NM_001243571.2:c.1321_1322dup
NM_016156.6:c.1537_1538dupMANE SELECT
NM_201278.3:c.1321_1322dup
NM_201281.3:c.1321_1322dup
NP_001230500.1:p.Ser442fs
NP_057240.3:p.Ser514fs
NP_958435.1:p.Ser442fs
NP_958438.1:p.Ser442fs
LRG_257:g.91056TA[3]
NC_000011.9:g.95571312_95571313insTA
NC_000011.9:g.95571313TA[3]
NM_016156.5:c.1537_1538dupTA

Protein change:

S442fs

Links:

dbSNP: rs1555057316

NCBI 1000 Genomes Browser:

rs1555057316

Molecular consequence:

NM_001243571.2:c.1321_1322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_016156.6:c.1537_1538dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_201278.3:c.1321_1322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_201281.3:c.1321_1322dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4
Synonyms:: Charcot-Marie-Tooth, Type 4
Identifiers:: MONDO: MONDO:0018995; MedGen: C4082197

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000545486	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 5, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10802647, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545486

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 5, 2020)

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

Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2.

Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, Christodoulou K, Hausmanowa-Petrusewicz I, Mandich P, Schenone A, Gambardella A, Bono F, Quattrone A, Devoto M, Monaco AP.

Nat Genet. 2000 May;25(1):17-9.

PubMed [citation]

PMID:: 10802647

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, SCV000545486.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MTMR2 are known to be pathogenic (PMID: 10802647). This variant has not been reported in the literature in individuals with MTMR2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser514Thrfs*32) in the MTMR2 gene. It is expected to result in an absent or disrupted protein product.

#	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

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