NM_014874.4(MFN2):c.284G>A (p.Arg95Lys) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 18, 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:: RCV001349707.7

Allele description [Variation Report for NM_014874.4(MFN2):c.284G>A (p.Arg95Lys)]

NM_014874.4(MFN2):c.284G>A (p.Arg95Lys)

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.284G>A (p.Arg95Lys)

HGVS:

NC_000001.11:g.11992663G>A
NG_007945.1:g.17483G>A
NM_001127660.2:c.284G>A
NM_014874.4:c.284G>AMANE SELECT
NP_001121132.1:p.Arg95Lys
NP_055689.1:p.Arg95Lys
LRG_255:g.17483G>A
NC_000001.10:g.12052720G>A

Protein change:

R95K

Links:

dbSNP: rs1638740596

NCBI 1000 Genomes Browser:

rs1638740596

Molecular consequence:

NM_001127660.2:c.284G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014874.4:c.284G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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PREDICTED: Zalophus californianus ST6 N-acetylgalactosaminide alpha-2,6-sialyltr...
PREDICTED: Zalophus californianus ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2), transcript variant X1, mRNA
gi|1886030748|ref|XM_027625363.2|

Nucleotide
Mus musculus chromatin target of PRMT1 (Chtop), transcript variant 1, mRNA
Mus musculus chromatin target of PRMT1 (Chtop), transcript variant 1, mRNA
gi|657940857|ref|NM_001293776.1|

Nucleotide
Haptosquilla trispinosa voucher LIRS06-24 28S ribosomal RNA gene, partial sequen...
Haptosquilla trispinosa voucher LIRS06-24 28S ribosomal RNA gene, partial sequence
gi|302320948|gb|HM180063.1|

Nucleotide
Portulaca oleracea isolate XW_2022a chromosome 9, whole genome shotgun sequence
Portulaca oleracea isolate XW_2022a chromosome 9, whole genome shotgun sequence
gi|2476876132|gb|CM055876.1||gnl|WG FYH|LG09

Nucleotide
RecName: Full=StAR-related lipid transfer protein 4; AltName: Full=START domain-...
RecName: Full=StAR-related lipid transfer protein 4; AltName: Full=START domain-containing protein 4; Short=StARD4
gi|25091318|sp|Q99JV5.1|STAR4_MOUSE

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001544062	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001544062

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001544062.4

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1045318). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 95 of the MFN2 protein (p.Arg95Lys). This variant disrupts the p.Arg95 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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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