NM_002180.3(IGHMBP2):c.891del (p.Lys298fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 7, 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:: RCV002680749.3

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.891del (p.Lys298fs)]

NM_002180.3(IGHMBP2):c.891del (p.Lys298fs)

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.891del (p.Lys298fs)

HGVS:

NC_000011.10:g.68915002del
NG_007976.1:g.16152del
NM_002180.3:c.891delMANE SELECT
NP_002171.2:p.Lys298Argfs
NP_002171.2:p.Lys298fs
LRG_250t1:c.891del
LRG_250:g.16152del
LRG_250p1:p.Lys298Argfs
NC_000011.9:g.68682469del
NC_000011.9:g.68682470del
NM_002180.2:c.891delG

Protein change:

K298fs

Molecular consequence:

NM_002180.3:c.891del - 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

Recent activity

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beta subunit of RNA polymerase, partial (chloroplast) [Badula decumbens]
beta subunit of RNA polymerase, partial (chloroplast) [Badula decumbens]
gi|610505934|emb|CCX28525.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002979942	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 7, 2022)	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

SCV002979942

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 7, 2022)

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, SCV002979942.2

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

Description

This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. This sequence change creates a premature translational stop signal (p.Lys298Argfs*8) 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). This variant is not present in population databases (gnomAD no frequency). 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

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