NM_002180.3(IGHMBP2):c.2752C>T (p.Arg918Cys) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Apr 18, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000798594.2

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.2752C>T (p.Arg918Cys)]

NM_002180.3(IGHMBP2):c.2752C>T (p.Arg918Cys)

Gene:
IGHMBP2:immunoglobulin mu DNA binding protein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.3
Genomic location:
Preferred name:
NM_002180.3(IGHMBP2):c.2752C>T (p.Arg918Cys)
HGVS:
  • NC_000011.10:g.68938322C>T
  • NG_007976.1:g.39472C>T
  • NM_002180.2:c.2752C>T
  • NM_002180.3:c.2752C>TMANE SELECT
  • NP_002171.2:p.Arg918Cys
  • NP_002171.2:p.Arg918Cys
  • LRG_250t1:c.2752C>T
  • LRG_250:g.39472C>T
  • LRG_250p1:p.Arg918Cys
  • NC_000011.9:g.68705790C>T
Protein change:
R918C
Links:
dbSNP: rs199962477
NCBI 1000 Genomes Browser:
rs199962477
Molecular consequence:
  • NM_002180.2:c.2752C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002180.3:c.2752C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spinal muscular atrophy, distal, autosomal recessive, 1 (DSMA1)
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 (CMT2S)
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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000938217Invitaecriteria provided, single submitter
Uncertain significance
(Apr 18, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Genetic heterogeneity of motor neuropathies.

Bansagi B, Griffin H, Whittaker RG, Antoniadi T, Evangelista T, Miller J, Greenslade M, Forester N, Duff J, Bradshaw A, Kleinle S, Boczonadi V, Steele H, Ramesh V, Franko E, Pyle A, Lochm├╝ller H, Chinnery PF, Horvath R.

Neurology. 2017 Mar 28;88(13):1226-1234. doi: 10.1212/WNL.0000000000003772. Epub 2017 Mar 1.

PubMed [citation]
PMID:
28251916
PMCID:
PMC5373778

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000938217.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with cysteine at codon 918 of the IGHMBP2 protein (p.Arg918Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs199962477, ExAC 0.01%). This variant has been observed in the heterozygous state in a family affected with hereditary motor neuropathy (PMID: 28251916). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

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