2-27309851-TCTGACCGTTCCAGGGTCAAGCTGCATCACTGCAAGGTGGAAACGATGGAGTGAGGCAGGCTTAGAGCCGATGTGCCTTCCAGGACAGGTAGGAGTTCCAGATAACAGCAACACATTGGACAACGGCCAACCTAAGGAACAGGAATAAC-T

Variant names:

• chr2-27309851-TCTGACCGTTCCAGGGTCAAGCTGCATCACTGCAAGGTGGAAACGATGGAGTGAGGCAGGCTTAGAGCCGATGTGCCTTCCAGGACAGGTAGGAGTTCCAGATAACAGCAACACATTGGACAACGGCCAACCTAAGGAACAGGAATAAC-T
• NM_002437.5:c.462-18_*60del

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_002437.5(MPV17):​c.460-18_*60del variant causes a splice acceptor, splice region, 3 prime UTR, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MPV17 NM_002437.5 splice_acceptor, splice_region, 3_prime_UTR, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.750

Genes affected

MPV17 (HGNC:7224): (mitochondrial inner membrane protein MPV17) This gene encodes a mitochondrial inner membrane protein that is implicated in the metabolism of reactive oxygen species. Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates 1.007561436672968 fraction of the gene.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-27309851-TCTGACCGTTCCAGGGTCAAGCTGCATCACTGCAAGGTGGAAACGATGGAGTGAGGCAGGCTTAGAGCCGATGTGCCTTCCAGGACAGGTAGGAGTTCCAGATAACAGCAACACATTGGACAACGGCCAACCTAAGGAACAGGAATAAC-T is Pathogenic according to our data. Variant chr2-27309851-TCTGACCGTTCCAGGGTCAAGCTGCATCACTGCAAGGTGGAAACGATGGAGTGAGGCAGGCTTAGAGCCGATGTGCCTTCCAGGACAGGTAGGAGTTCCAGATAACAGCAACACATTGGACAACGGCCAACCTAAGGAACAGGAATAAC-T is described in ClinVar as [Pathogenic]. Clinvar id is 2672805.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPV17	NM_002437.5	c.462-18_*60del	p.Arg154fs	frameshift_variant, stop_lost, splice_region_variant	Exon 8 of 8	ENST00000380044.6	NP_002428.1
MPV17	NM_002437.5	c.460-18_*60del		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_variant	Exon 8 of 8	ENST00000380044.6	NP_002428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPV17	ENST00000380044.6	c.462-18_*60del	p.Arg154fs	frameshift_variant, stop_lost, splice_region_variant	Exon 8 of 8	1	NM_002437.5	ENSP00000369383.1
MPV17	ENST00000380044	c.460-18_*60del		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_variant	Exon 8 of 8	1	NM_002437.5	ENSP00000369383.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MPV17: PVS1, PM2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27532719;