NM_014874.4(MFN2):c.245del (p.Leu82fs) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 30, 2023
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:: RCV001863268.4

Allele description [Variation Report for NM_014874.4(MFN2):c.245del (p.Leu82fs)]

NM_014874.4(MFN2):c.245del (p.Leu82fs)

Gene:

MFN2:mitofusin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_014874.4(MFN2):c.245del (p.Leu82fs)

HGVS:

NC_000001.11:g.11992624del
NG_007945.1:g.17444del
NM_001127660.2:c.245del
NM_014874.4:c.245delMANE SELECT
NP_001121132.1:p.Leu82fs
NP_055689.1:p.Leu82fs
LRG_255:g.17444del
NC_000001.10:g.12052681del

Protein change:

L82fs

Links:

dbSNP: rs2100812695

NCBI 1000 Genomes Browser:

rs2100812695

Molecular consequence:

NM_001127660.2:c.245del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014874.4:c.245del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002110164	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 30, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16714318, 16835246, 21715711, 23781337, 26955893, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002110164

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 30, 2023)

germline

clinical testing

PubMed (6)
[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

MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2.

Verhoeven K, Claeys KG, Züchner S, Schröder JM, Weis J, Ceuterick C, Jordanova A, Nelis E, De Vriendt E, Van Hul M, Seeman P, Mazanec R, Saifi GM, Szigeti K, Mancias P, Butler IJ, Kochanski A, Ryniewicz B, De Bleecker J, Van den Bergh P, Verellen C, Van Coster R, et al.

Brain. 2006 Aug;129(Pt 8):2093-102. Epub 2006 May 19.

PubMed [citation]

PMID:: 16714318

Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations.

Chung KW, Kim SB, Park KD, Choi KG, Lee JH, Eun HW, Suh JS, Hwang JH, Kim WK, Seo BC, Kim SH, Son IH, Kim SM, Sunwoo IN, Choi BO.

Brain. 2006 Aug;129(Pt 8):2103-18. Epub 2006 Jul 10.

PubMed [citation]

PMID:: 16835246

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002110164.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Leu82Hisfs*4) in the MFN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MFN2 are known to be pathogenic (PMID: 16714318, 16835246, 21715711, 23781337, 26955893). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1353202). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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