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NM_002180.3(IGHMBP2):c.790C>T (p.Arg264Cys) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 20, 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:
RCV001972476.6

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.790C>T (p.Arg264Cys)]

NM_002180.3(IGHMBP2):c.790C>T (p.Arg264Cys)

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.790C>T (p.Arg264Cys)
HGVS:
  • NC_000011.10:g.68914901C>T
  • NG_007976.1:g.16051C>T
  • NM_002180.2:c.790C>T
  • NM_002180.3:c.790C>TMANE SELECT
  • NP_002171.2:p.Arg264Cys
  • LRG_250t1:c.790C>T
  • LRG_250:g.16051C>T
  • NC_000011.9:g.68682369C>T
Protein change:
R264C
Links:
dbSNP: rs139497493
NCBI 1000 Genomes Browser:
rs139497493
Molecular consequence:
  • NM_002180.3:c.790C>T - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002245733Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 20, 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

Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability.

Antoniadi T, Buxton C, Dennis G, Forrester N, Smith D, Lunt P, Burton-Jones S.

BMC Med Genet. 2015 Sep 21;16:84. doi: 10.1186/s12881-015-0224-8.

PubMed [citation]
PMID:
26392352
PMCID:
PMC4578331

Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies.

Dohrn MF, Glöckle N, Mulahasanovic L, Heller C, Mohr J, Bauer C, Riesch E, Becker A, Battke F, Hörtnagel K, Hornemann T, Suriyanarayanan S, Blankenburg M, Schulz JB, Claeys KG, Gess B, Katona I, Ferbert A, Vittore D, Grimm A, Wolking S, Schöls L, et al.

J Neurochem. 2017 Dec;143(5):507-522. doi: 10.1111/jnc.14217. Epub 2017 Nov 7.

PubMed [citation]
PMID:
28902413
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002245733.3

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 264 of the IGHMBP2 protein (p.Arg264Cys). This variant is present in population databases (rs139497493, gnomAD 0.03%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (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: 1456797). 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. This variant disrupts the p.Arg264 amino acid residue in IGHMBP2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26392352, 28902413; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024