U.S. flag

An official website of the United States government

NM_002180.3(IGHMBP2):c.2540del (p.Gln847fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 4, 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:
RCV001204582.8

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.2540del (p.Gln847fs)]

NM_002180.3(IGHMBP2):c.2540del (p.Gln847fs)

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.2540del (p.Gln847fs)
HGVS:
  • NC_000011.10:g.68937020del
  • NG_007976.1:g.38170del
  • NM_002180.3:c.2540delMANE SELECT
  • NP_002171.2:p.Gln847fs
  • LRG_250t1:c.2540del
  • LRG_250:g.38170del
  • NC_000011.9:g.68704488del
  • NM_002180.2:c.2540del
  • NM_002180.3:c.2540delAMANE SELECT
Protein change:
Q847fs
Links:
dbSNP: rs1225532037
NCBI 1000 Genomes Browser:
rs1225532037
Molecular consequence:
  • NM_002180.3:c.2540del - frameshift variant - [Sequence Ontology: SO:0001589]
Functional consequence:
mutation affecting reading frame [Sequence Ontology: SO:1000064]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001375795Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 4, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical and mutational characteristics of spinal muscular atrophy with respiratory distress type 1 in The Netherlands.

Stalpers XL, Verrips A, Poll-The BT, Cobben JM, Snoeck IN, de Coo IF, Brooks A, Bulk S, Gooskens R, Fock A, Verschuuren-Bemelmans C, Sinke RJ, de Visser M, Lemmink HH.

Neuromuscul Disord. 2013 Jun;23(6):461-8. doi: 10.1016/j.nmd.2013.03.002. Epub 2013 Apr 6.

PubMed [citation]
PMID:
23566544

Autosomal recessive axonal polyneuropathy in a sibling pair due to a novel homozygous mutation in IGHMBP2.

Wagner JD, Huang L, Tetreault M, Majewski J, Boycott KM, Bulman DE; Care4Rare Canada Consortium., Dyment DA, McMillan HJ.

Neuromuscul Disord. 2015 Oct;25(10):794-9. doi: 10.1016/j.nmd.2015.07.017. Epub 2015 Aug 5.

PubMed [citation]
PMID:
26298607
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001375795.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the IGHMBP2 protein in which other variant(s) (p.Arg971Glufs*4, p.Lys868Profs*109) have been determined to be pathogenic (PMID: 23566544, 26298607). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 935895). This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change creates a premature translational stop signal (p.Gln847Argfs*131) in the IGHMBP2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 147 amino acid(s) of the IGHMBP2 protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024