NM_002180.3(IGHMBP2):c.1562A>G (p.His521Arg) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Sep 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:
RCV000554835.3

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.1562A>G (p.His521Arg)]

NM_002180.3(IGHMBP2):c.1562A>G (p.His521Arg)

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.1562A>G (p.His521Arg)
HGVS:
  • NC_000011.10:g.68934488A>G
  • NG_007976.1:g.35638A>G
  • NM_002180.2:c.1562A>G
  • NM_002180.3:c.1562A>GMANE SELECT
  • NP_002171.2:p.His521Arg
  • NP_002171.2:p.His521Arg
  • LRG_250t1:c.1562A>G
  • LRG_250:g.35638A>G
  • LRG_250p1:p.His521Arg
  • NC_000011.9:g.68701956A>G
Protein change:
H521R
Links:
dbSNP: rs1555247556
NCBI 1000 Genomes Browser:
rs1555247556
Molecular consequence:
  • NM_002180.2:c.1562A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002180.3:c.1562A>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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000642313Invitaecriteria provided, single submitter
Uncertain significance
(Sep 18, 2019)
germlineclinical 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

Citations

PubMed

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, SCV000642313.3

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

Description

This sequence change replaces histidine with arginine at codon 521 of the IGHMBP2 protein (p.His521Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IGHMBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 466580). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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: Oct 30, 2021

Support Center