NM_002180.3(IGHMBP2):c.763_767del (p.Leu255fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 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:: RCV001383330.5

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.763_767del (p.Leu255fs)]

NM_002180.3(IGHMBP2):c.763_767del (p.Leu255fs)

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.763_767del (p.Leu255fs)

HGVS:

NC_000011.10:g.68914874_68914878del
NG_007976.1:g.16024_16028del
NM_002180.3:c.763_767delMANE SELECT
NP_002171.2:p.Leu255fs
LRG_250:g.16024_16028del
NC_000011.9:g.68682340_68682344del
NC_000011.9:g.68682342_68682346del

Protein change:

L255fs

Links:

dbSNP: rs2154007211

NCBI 1000 Genomes Browser:

rs2154007211

Molecular consequence:

NM_002180.3:c.763_767del - 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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LOC100240734 [Homo sapiens]
LOC100240734 [Homo sapiens]
Gene ID:100240734

Gene
Gene Links for GEO Profiles (Select 65681862) (1)
Gene
HOXC11 homeobox C11 [Homo sapiens]
HOXC11 homeobox C11 [Homo sapiens]
Gene ID:3227

Gene
Gene Links for GEO Profiles (Select 65649192) (1)
Gene
Homologene neighbors for GEO Profiles (Select 65649305) (0)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001582419	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 14681881, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001582419

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 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

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

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, SCV001582419.4

#	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 IGHMBP2 are known to be pathogenic (PMID: 14681881). This variant has not been reported in the literature in individuals with IGHMBP2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu255Serfs*3) in the IGHMBP2 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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