NM_002437.5(MPV17):c.280-1dup AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Sep 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000486235.15

Allele description

NM_002437.5(MPV17):c.280-1dup

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_002437.5(MPV17):c.280-1dup

HGVS:

NC_000002.12:g.27312590dup
NG_008075.1:g.14980dup
NG_033055.1:g.679dup
NM_002437.5:c.280-1dupMANE SELECT
NM_002437.5:c.284dup
NC_000002.11:g.27535451_27535452insC
NC_000002.11:g.27535457dup
NM_002437.4:c.284dup
NM_002437.4:c.284dupG
NM_002437.5:c.284dupMANE SELECT
NM_002437.5:c.284dupGMANE SELECT

Links:

dbSNP: rs766160589

NCBI 1000 Genomes Browser:

rs766160589

Molecular consequence:

NM_002437.5:c.280-1dup - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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MAG: Actinobacteria bacterium HGW-Actinobacteria-1 bjp_ig2102_scaffold_933, whol...
MAG: Actinobacteria bacterium HGW-Actinobacteria-1 bjp_ig2102_scaffold_933, whole genome shotgun sequence
gi|1309179624|gb|PHFB01000018.1||gn :PHFB01|bjp_ig2102_scaffold_933

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000345002	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Aug 16, 2016)	germline	clinical testing	Citation Link,
SCV000565695	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 15, 2015)	germline	clinical testing	Citation Link,
SCV001585137	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23714749, 27848944, 29282788, 28492532
SCV002520078	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 16, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27848944, 33258288, 29282788, 25741868
SCV003819652	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene.

Uusimaa J, Evans J, Smith C, Butterworth A, Craig K, Ashley N, Liao C, Carver J, Diot A, Macleod L, Hargreaves I, Al-Hussaini A, Faqeih E, Asery A, Al Balwi M, Eyaid W, Al-Sunaid A, Kelly D, van Mourik I, Ball S, Jarvis J, Mulay A, et al.

Eur J Hum Genet. 2014 Feb;22(2):184-91. doi: 10.1038/ejhg.2013.112. Epub 2013 May 29.

PubMed [citation]

PMID:: 23714749
PMCID:: PMC3895632

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

See all PubMed Citations (6)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000345002.3

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

#	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		1	not provided	not provided	not provided

From GeneDx, SCV000565695.3

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

Description

The c.284dupG variant ispredicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this duplication has not been previously reported to our knowledge, itis expected to be a pathogenic variant.

#	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		not provided	not provided	not provided	not provided

From Invitae, SCV001585137.4

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

Description

This sequence change creates a premature translational stop signal (p.Phe96Leufs*17) in the MPV17 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPV17 are known to be pathogenic (PMID: 23714749). This variant is present in population databases (rs766160589, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of mitochondrial DNA maintenance defect (PMID: 27848944, 29282788). ClinVar contains an entry for this variant (Variation ID: 290443). 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

From Mayo Clinic Laboratories, Mayo Clinic, SCV002520078.1

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

Description

PVS1, PS4_moderate, PM2, PM3

#	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

From Revvity Omics, Revvity, SCV003819652.2

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

#	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: Aug 4, 2024

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