NM_002437.5(MPV17):c.106C>T (p.Gln36Ter) AND Charcot-Marie-Tooth disease, axonal, type 2EE

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 22, 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:: RCV003320355.3

Allele description [Variation Report for NM_002437.5(MPV17):c.106C>T (p.Gln36Ter)]

NM_002437.5(MPV17):c.106C>T (p.Gln36Ter)

Gene:

MPV17:mitochondrial inner membrane protein MPV17 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_002437.5(MPV17):c.106C>T (p.Gln36Ter)

HGVS:

NC_000002.12:g.27313074G>A
NG_008075.1:g.14491C>T
NG_033055.1:g.190C>T
NM_002437.5:c.106C>TMANE SELECT
NP_002428.1:p.Gln36Ter
NC_000002.11:g.27535941G>A
NM_002437.4:c.106C>T
c.106C>T
p.Q36X

Protein change:

Q36*

Links:

dbSNP: rs754051090

NCBI 1000 Genomes Browser:

rs754051090

Molecular consequence:

NM_002437.5:c.106C>T - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

protein truncation [Variation Ontology: 0015]

Condition(s)

Name:: Charcot-Marie-Tooth disease, axonal, type 2EE
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2EE
Identifiers:: MONDO: MONDO:0032728; MedGen: C5193076; OMIM: 618400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003930386	Neurogenomics Lab, Neuroscience Institute, University Of Cape Town	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 22, 2024)	germline	research	PubMed (4) [See all records that cite these PMIDs] 37712079, 29318572, 30782936, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003930386

Neurogenomics Lab, Neuroscience Institute, University Of Cape Town

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 22, 2024)

germline

research

PubMed (4)
[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	4	4	not provided	not provided	not provided	research

Citations

PubMed

The mutational profile in a South African cohort with inherited neuropathies and spastic paraplegia.

Mahungu AC, Steyn E, Floudiotis N, Wilson LA, Vandrovcova J, Reilly MM, Record CJ, Benatar M, Wu G, Raga S, Wilmshurst JM, Naidu K, Hanna M, Nel M, Heckmann JM.

Front Neurol. 2023;14:1239725. doi: 10.3389/fneur.2023.1239725.

PubMed [citation]

PMID:: 37712079
PMCID:: PMC10497947

Identification of a single MPV17 nonsense-associated altered splice variant in 24 South African infants with mitochondrial neurohepatopathy.

Meldau S, De Lacy RJ, Riordan GTM, Goddard EA, Pillay K, Fieggen KJ, Marais AD, Van der Watt GF.

Clin Genet. 2018 May;93(5):1093-1096. doi: 10.1111/cge.13208. Epub 2018 Mar 25.

PubMed [citation]

PMID:: 29318572

See all PubMed Citations (4)

Details of each submission

From Neurogenomics Lab, Neuroscience Institute, University Of Cape Town, SCV003930386.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	research	PubMed (4)

Description

All 4 probands carry a second heterozygous MPV17 VUS NP_002428.1:p.Arg125Trp (not confirmed in trans).

Description

PM2_supporting: this variant is absent from gnomAD v4.0 (adequate coverage >20X confirmed) while it has a MAF of 0.007 and 0.015 in two independent control samples from South Africa (PMID 29318572 and PMID 30782936 respectively). PVS1 not assigned as loss of gene function is not an established pathogenic mechanism for MPV17-related CMT2EE; the majority of MPV17 variants associated with CMT2EE are homozygous missense variants while the single reported homozygous non-frameshift deletion, p.Asp126_Tyr136del, removes <10% of the MPV17 protein. Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	4	not provided

Last Updated: Jun 2, 2024

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