NM_014874.4(MFN2):c.1126A>G (p.Met376Val) AND Charcot-Marie-Tooth disease type 2A2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 22, 2022
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:: RCV002051828.9

Allele description [Variation Report for NM_014874.4(MFN2):c.1126A>G (p.Met376Val)]

NM_014874.4(MFN2):c.1126A>G (p.Met376Val)

Gene:

MFN2:mitofusin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_014874.4(MFN2):c.1126A>G (p.Met376Val)

HGVS:

NC_000001.11:g.12002069A>G
NG_007945.1:g.26889A>G
NM_001127660.2:c.1126A>G
NM_014874.4:c.1126A>GMANE SELECT
NP_001121132.1:p.Met376Val
NP_055689.1:p.Met376Val
NP_055689.1:p.Met376Val
LRG_255t1:c.1126A>G
LRG_255:g.26889A>G
LRG_255p1:p.Met376Val
NC_000001.10:g.12062126A>G
NM_014874.3:c.1126A>G

Protein change:

M376V

Links:

dbSNP: rs863224967

NCBI 1000 Genomes Browser:

rs863224967

Molecular consequence:

NM_001127660.2:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014874.4:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2A2
Synonyms:: CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2A2; CHARCOT-MARIE-TOOTH DISEASE, NEURONAL, TYPE 2A2; HEREDITARY MOTOR AND SENSORY NEUROPATHY IIA2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012231; MedGen: C4721887; Orphanet: 99947; OMIM: 609260

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002318905	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 22, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 26801520, 16762064, 19889647, 16835246, 22926664, 24957169, 28251916, 22851605, 22492563, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002318905

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 22, 2022)

germline

clinical testing

PubMed (10)
[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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Xie Y, Li X, Liu L, Hu Z, Huang S, Zhan Y, Zi X, Xia K, Tang B, Zhang R.

J Peripher Nerv Syst. 2016 Mar;21(1):38-44. doi: 10.1111/jns.12159.

PubMed [citation]

PMID:: 26801520

Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2).

Engelfried K, Vorgerd M, Hagedorn M, Haas G, Gilles J, Epplen JT, Meins M.

BMC Med Genet. 2006 Jun 8;7:53.

PubMed [citation]

PMID:: 16762064
PMCID:: PMC1524942

See all PubMed Citations (10)

Details of each submission

From 3billion, SCV002318905.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (10)

Description

Same or different nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000217161). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 19889647, 22926664, 26801520, 22492563, 22851605, 28251916). Different missense changes at the same codon have been reported to be associated with MFN2 related disorder (PMID:16835246,24957169,16762064). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.794>=0.6, 3CNET: 0.806>=0.75). A missense variant is a common mechanism. It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Nov 3, 2024

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