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NM_002180.3(IGHMBP2):c.1156T>C (p.Trp386Arg) AND multiple conditions

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Nov 4, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000695581.11

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.1156T>C (p.Trp386Arg)]

NM_002180.3(IGHMBP2):c.1156T>C (p.Trp386Arg)

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.1156T>C (p.Trp386Arg)
HGVS:
  • NC_000011.10:g.68929278T>C
  • NG_007976.1:g.30428T>C
  • NM_002180.3:c.1156T>CMANE SELECT
  • NP_002171.2:p.Trp386Arg
  • NP_002171.2:p.Trp386Arg
  • LRG_250t1:c.1156T>C
  • LRG_250:g.30428T>C
  • LRG_250p1:p.Trp386Arg
  • NC_000011.9:g.68696746T>C
  • NM_002180.2:c.1156T>C
Protein change:
W386R
Links:
dbSNP: rs759641927
NCBI 1000 Genomes Browser:
rs759641927
Molecular consequence:
  • NM_002180.3:c.1156T>C - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000824090Invitae
criteria provided, single submitter

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

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

SCV000893231Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Oct 31, 2018)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis.

Guenther UP, Varon R, Schlicke M, Dutrannoy V, Volk A, Hübner C, von Au K, Schuelke M.

Hum Mutat. 2007 Aug;28(8):808-15.

PubMed [citation]
PMID:
17431882

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)
PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]
PMCID:
PMC4544753
PMID:
25741868
DOI:
10.1038/gim.2015.30

Details of each submission

From Invitae, SCV000824090.7

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

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 386 of the IGHMBP2 protein (p.Trp386Arg). This variant is present in population databases (rs759641927, gnomAD 0.006%). This missense change has been observed in individual(s) with spinal muscular atrophy with respiratory distress (SMARD), Charcot-Marie-Tooth disease type 2 (CMT2), and with hereditary motor and sensory neuropathy (PMID: 17431882, 25439726; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 573815). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IGHMBP2 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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

From Fulgent Genetics, Fulgent Genetics, SCV000893231.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 17, 2024