M-12264-C-T

Position:

• chrM-12264-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2 PP3 PP5_Very_Strong

The ENST00000387449.1(MT-TS2):​n.58C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: MT-TS2 ENST00000387449.1 non_coding_transcript_exon
• Scores: Mitotip Pathogenic 17
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2 Multisystem-Disease-with-Cataracts-/-Myopathy+epilepsy+DEAF+atypical-autism
• Conservation: PhyloP100: -0.0400

Genes affected

MT-TS2 (HGNC:7498): (mitochondrially encoded tRNA serine 2 (AGU/C))

TRNS2 (HGNC:):

MT-TL2 (HGNC:7491): (mitochondrially encoded tRNA leucine 2 (CUN))

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP3: Mitotip and hmtvar scores support pathogenic criterium.
• PP5: Variant M-12264-C-T is Pathogenic according to our data. Variant chrM-12264-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 690178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNS2	TRNS2.1	n.58C>T		non_coding_transcript_exon_variant	1/1
TRNL2	TRNL2.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TS2	ENST00000387449.1	n.58C>T		non_coding_transcript_exon_variant	1/1
MT-TL2	ENST00000387456.1			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0 AC: 0

Mitomap

Multisystem-Disease-with-Cataracts-/-Myopathy+epilepsy+DEAF+atypical-autism

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	Jul 12, 2019	The NC_012920.1:m.12264C>T variant in MT-TS2 gene is interpreted to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PM7, PM9, PM10 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Pathogenic	17
Hmtvar	Pathogenic	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603223642; hg19: chrM-12265;