NM_002180.3(IGHMBP2):c.1489G>A (p.Gly497Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 2021
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:: RCV001037478.5

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.1489G>A (p.Gly497Arg)]

NM_002180.3(IGHMBP2):c.1489G>A (p.Gly497Arg)

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.1489G>A (p.Gly497Arg)

HGVS:

NC_000011.10:g.68933865G>A
NG_007976.1:g.35015G>A
NM_002180.3:c.1489G>AMANE SELECT
NP_002171.2:p.Gly497Arg
LRG_250t1:c.1489G>A
LRG_250:g.35015G>A
NC_000011.9:g.68701333G>A
NM_002180.2:c.1489G>A

Protein change:

G497R

Links:

dbSNP: rs764111837

NCBI 1000 Genomes Browser:

rs764111837

Molecular consequence:

NM_002180.3:c.1489G>A - 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

Recent activity

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P24 (9)
Conserved Domains
MRET_0219 [Malassezia restricta]
MRET_0219 [Malassezia restricta]
Gene ID:38736985

Gene
Intestinal Obstruction
Intestinal Obstruction
Any impairment, arrest, or reversal of the normal flow of INTESTINAL CONTENTS toward the ANAL CANAL.<br/>

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200893	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28065684, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200893

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Liu L, Li X, Hu Z, Mao X, Zi X, Xia K, Tang B, Zhang R.

Neuromuscul Disord. 2017 Feb;27(2):193-199. doi: 10.1016/j.nmd.2016.11.008. Epub 2016 Nov 18.

PubMed [citation]

PMID:: 28065684

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001200893.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine with arginine at codon 497 of the IGHMBP2 protein (p.Gly497Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs764111837, ExAC 0.005%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease, type 2 (PMID: 28065684). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 21, 2023

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