NM_002180.3(IGHMBP2):c.734A>G (p.Asn245Ser) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Apr 24, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000642625.2

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.734A>G (p.Asn245Ser)]

NM_002180.3(IGHMBP2):c.734A>G (p.Asn245Ser)

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.734A>G (p.Asn245Ser)
HGVS:
  • NC_000011.10:g.68914845A>G
  • NG_007976.1:g.15995A>G
  • NM_002180.3:c.734A>GMANE SELECT
  • NP_002171.2:p.Asn245Ser
  • NP_002171.2:p.Asn245Ser
  • LRG_250t1:c.734A>G
  • LRG_250:g.15995A>G
  • LRG_250p1:p.Asn245Ser
  • NC_000011.9:g.68682313A>G
  • NM_002180.2:c.734A>G
Protein change:
N245S
Links:
dbSNP: rs1555243999
NCBI 1000 Genomes Browser:
rs1555243999
Molecular consequence:
  • NM_002180.3:c.734A>G - 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
SCV000764312Invitaecriteria provided, single submitter
Uncertain significance
(Apr 24, 2018)
germlineclinical testing

PubMed (3)
[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

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

Infantile spinal muscular atrophy with respiratory distress type I presenting without respiratory involvement: Novel mutations and review of the literature.

Luan X, Huang X, Liu X, Zhou H, Chen S, Cao L.

Brain Dev. 2016 Aug;38(7):685-9. doi: 10.1016/j.braindev.2016.02.001. Epub 2016 Feb 24. Review.

PubMed [citation]
PMID:
26922252
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000764312.2

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

Description

This sequence change replaces asparagine with serine at codon 245 of the IGHMBP2 protein (p.Asn245Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the heterozygous state in individuals affected with Charcot-Marie-Tooth (CMT) disease type 2 and gait difficulty (PMID: 25439726, 26922252). This variant has been reported in combination with other IGHMBP2 variants in an individual affected with CMT disease (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Dec 4, 2021

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