U.S. flag

An official website of the United States government

NM_001303256.3(MORC2):c.839C>T (p.Thr280Met) AND Charcot-Marie-Tooth disease axonal type 2Z

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 24, 2024
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:
RCV000652691.7

Allele description [Variation Report for NM_001303256.3(MORC2):c.839C>T (p.Thr280Met)]

NM_001303256.3(MORC2):c.839C>T (p.Thr280Met)

Gene:
MORC2:MORC family CW-type zinc finger 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q12.2
Genomic location:
Preferred name:
NM_001303256.3(MORC2):c.839C>T (p.Thr280Met)
HGVS:
  • NC_000022.11:g.30940823G>A
  • NG_046752.1:g.32675C>T
  • NM_001303256.3:c.839C>TMANE SELECT
  • NM_001303257.2:c.839C>T
  • NM_014941.3:c.653C>T
  • NP_001290185.1:p.Thr280Met
  • NP_001290186.1:p.Thr280Met
  • NP_055756.1:p.Thr218Met
  • NC_000022.10:g.31336810G>A
  • NM_001303256.2:c.839C>T
  • NM_014941.2:c.653C>T
Protein change:
T218M
Links:
dbSNP: rs764379949
NCBI 1000 Genomes Browser:
rs764379949
Molecular consequence:
  • NM_001303256.3:c.839C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001303257.2:c.839C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014941.3:c.653C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Charcot-Marie-Tooth disease axonal type 2Z
Synonyms:
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2Z; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2Z
Identifiers:
MONDO: MONDO:0014736; MedGen: C5569025; OMIM: 616688

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
SCV000774562Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 24, 2024)
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, SCV000774562.5

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

Description

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 280 of the MORC2 protein (p.Thr280Met). This variant is present in population databases (rs764379949, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 542290). 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 MORC2 protein function with a positive predictive value of 95%. 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: May 1, 2024