NM_014874.4(MFN2):c.748del (p.Arg250fs) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 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:: RCV003582756.2

Allele description [Variation Report for NM_014874.4(MFN2):c.748del (p.Arg250fs)]

NM_014874.4(MFN2):c.748del (p.Arg250fs)

Gene:

MFN2:mitofusin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_014874.4(MFN2):c.748del (p.Arg250fs)

HGVS:

NC_000001.11:g.11999027del
NG_007945.1:g.23847del
NM_001127660.2:c.748del
NM_014874.4:c.748delMANE SELECT
NP_001121132.1:p.Arg250fs
NP_055689.1:p.Arg250Glyfs
NP_055689.1:p.Arg250fs
LRG_255t1:c.748del
LRG_255:g.23847del
LRG_255p1:p.Arg250Glyfs
NC_000001.10:g.12059082del
NC_000001.10:g.12059084del
NM_014874.3:c.748delC

Protein change:

R250fs

Molecular consequence:

NM_001127660.2:c.748del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014874.4:c.748del - 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
SCV004309941	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 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

SCV004309941

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 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, SCV004309941.1

#	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.Arg250Glyfs*7) 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MFN2-related conditions. This variant is present in population databases (rs754530491, gnomAD 0.003%).

#	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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