NM_002180.3(IGHMBP2):c.1693G>A (p.Asp565Asn) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Mar 6, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000705582.4

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.1693G>A (p.Asp565Asn)]

NM_002180.3(IGHMBP2):c.1693G>A (p.Asp565Asn)

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.1693G>A (p.Asp565Asn)
HGVS:
  • NC_000011.10:g.68935359G>A
  • NG_007976.1:g.36509G>A
  • NM_002180.3:c.1693G>AMANE SELECT
  • NP_002171.2:p.Asp565Asn
  • NP_002171.2:p.Asp565Asn
  • LRG_250t1:c.1693G>A
  • LRG_250:g.36509G>A
  • LRG_250p1:p.Asp565Asn
  • NC_000011.9:g.68702827G>A
  • NM_002180.2:c.1693G>A
Protein change:
D565N
Links:
dbSNP: rs770111639
NCBI 1000 Genomes Browser:
rs770111639
Molecular consequence:
  • NM_002180.3:c.1693G>A - 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
SCV000834584Invitaecriteria provided, single submitter
Likely pathogenic
(Mar 6, 2020)
germlineclinical testing

PubMed (5)
[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

Allelic heterogeneity of SMARD1 at the IGHMBP2 locus.

Maystadt I, Zarhrate M, Landrieu P, Boespflug-Tanguy O, Sukno S, Collignon P, Melki J, Verellen-Dumoulin C, Munnich A, Viollet L.

Hum Mutat. 2004 May;23(5):525-6.

PubMed [citation]
PMID:
15108294

Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1).

Grohmann K, Varon R, Stolz P, Schuelke M, Janetzki C, Bertini E, Bushby K, Muntoni F, Ouvrier R, Van Maldergem L, Goemans NM, Lochm├╝ller H, Eichholz S, Adams C, Bosch F, Grattan-Smith P, Navarro C, Neitzel H, Polster T, Topalo─člu H, Steglich C, Guenther UP, et al.

Ann Neurol. 2003 Dec;54(6):719-24.

PubMed [citation]
PMID:
14681881
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000834584.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces aspartic acid with asparagine at codon 565 of the IGHMBP2 protein (p.Asp565Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs770111639, ExAC 0.005%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with distal hereditary motor neuropathy, type VI (PMID: 15108294). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has been reported in combination with another IGHMBP2 variant in an individual affected with distal hereditary motor neuropathy, type VI (PMID: 22157136, 14681881). Experimental studies have shown that this missense change results in abolished helicase activity of the encoded IGHMBP2 protein (PMID: 19158098, 22157136). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Dec 4, 2021

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