NM_002180.3(IGHMBP2):c.2T>C (p.Met1Thr) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Dec 4, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000810966.1

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.2T>C (p.Met1Thr)]

NM_002180.3(IGHMBP2):c.2T>C (p.Met1Thr)

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.2T>C (p.Met1Thr)
HGVS:
  • NC_000011.10:g.68903954T>C
  • NG_007976.1:g.5104T>C
  • NM_002180.2:c.2T>C
  • NM_002180.3:c.2T>CMANE SELECT
  • NP_002171.2:p.Met1Thr
  • NP_002171.2:p.Met1Thr
  • LRG_250t1:c.2T>C
  • LRG_250:g.5104T>C
  • LRG_250p1:p.Met1Thr
  • NC_000011.9:g.68671422T>C
Protein change:
M1T
Links:
dbSNP: rs886037759
NCBI 1000 Genomes Browser:
rs886037759
Molecular consequence:
  • NM_002180.3:c.2T>C - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_002180.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002180.3:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
initiation codon change [Variation Ontology: 0317] - Comment(s)

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
SCV000951208Invitaecriteria provided, single submitter
Likely pathogenic
(Dec 4, 2018)
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, SCV000951208.1

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

Description

This sequence change affects the initiator methionine of the IGHMBP2 mRNA. The next in-frame methionine is located at codon 338. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease or spinal muscular atrophy with respiratory distress (PMID: 26392352, 27450922). ClinVar contains an entry for this variant (Variation ID: 217448). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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: Oct 25, 2021

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