NM_002180.3(IGHMBP2):c.408_409del (p.Leu137fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 20, 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:: RCV003778310.2

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.408_409del (p.Leu137fs)]

NM_002180.3(IGHMBP2):c.408_409del (p.Leu137fs)

Gene:

IGHMBP2:immunoglobulin mu DNA binding protein 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q13.3

Genomic location:

Preferred name:

NM_002180.3(IGHMBP2):c.408_409del (p.Leu137fs)

HGVS:

NC_000011.10:g.68908296_68908297del
NG_007976.1:g.9446_9447del
NM_002180.3:c.408_409delMANE SELECT
NP_002171.2:p.Leu137Lysfs
NP_002171.2:p.Leu137fs
LRG_250t1:c.408_409del
LRG_250:g.9446_9447del
LRG_250p1:p.Leu137Lysfs
NC_000011.9:g.68675763_68675764del
NC_000011.9:g.68675764_68675765del
NM_002180.2:c.408_409delGT

Protein change:

L137fs

Molecular consequence:

NM_002180.3:c.408_409del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Autosomal recessive distal spinal muscular atrophy 1
Synonyms:: HMN VI; SPINAL MUSCULAR ATROPHY, DIAPHRAGMATIC; Spinal muscular atrophy with respiratory distress 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011436; MedGen: C1858517; Orphanet: 98920; OMIM: 604320

Name:: Charcot-Marie-Tooth disease axonal type 2S
Synonyms:: CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL RECESSIVE, TYPE 2S; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2S
Identifiers:: MONDO: MONDO:0014511; MedGen: C4015349; Orphanet: 443073; OMIM: 616155

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004610697	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 20, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 14681881, 25439726, 25568292, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004610697

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 20, 2023)

germline

clinical testing

PubMed (4)
[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

Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1).

Grohmann K, Varon R, Stolz P, Schuelke M, Janetzki C, Bertini E, Bushby K, Muntoni F, Ouvrier R, Van Maldergem L, Goemans NM, Lochmüller H, Eichholz S, Adams C, Bosch F, Grattan-Smith P, Navarro C, Neitzel H, Polster T, Topaloğlu H, Steglich C, Guenther UP, et al.

Ann Neurol. 2003 Dec;54(6):719-24.

PubMed [citation]

PMID:: 14681881

Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.

Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, et al.

Am J Hum Genet. 2014 Nov 6;95(5):590-601. doi: 10.1016/j.ajhg.2014.10.002. Epub 2014 Oct 30.

PubMed [citation]

PMID:: 25439726
PMCID:: PMC4225647

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004610697.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. This variant is present in population databases (rs767630646, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Leu137Lysfs*5) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IGHMBP2 are known to be pathogenic (PMID: 14681881, 25439726, 25568292).

#	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: Oct 26, 2024

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