M-12236-G-A

Position:

• chrM-12236-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4 BP6 BS1 BS2

The ENST00000387449.1(MT-TS2):​n.30G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0071 (AC: 436)
• Consequence: MT-TS2 ENST00000387449.1 non_coding_transcript_exon
• Scores: Mitotip Benign 2.0
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2 DEAF
• Conservation: PhyloP100: -0.453

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))

MT-TH (HGNC:7487): (mitochondrially encoded tRNA histidine)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Mitotip and hmtvar scores support benign criterium.
• BP6: Variant M-12236-G-A is Benign according to our data. Variant chrM-12236-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 440357.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.
• BS1: High frequency in mitomap database: 0.0070999996
• BS2: High AC in GnomadMitoHomoplasmic at 1592

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRNS2	TRNS2.1	n.30G>A		non_coding_transcript_exon_variant	1/1
TRNL2	TRNL2.1			upstream_gene_variant
TRNH	TRNH.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-TS2	ENST00000387449.1	n.30G>A		non_coding_transcript_exon_variant	1/1
MT-TL2	ENST00000387456.1			upstream_gene_variant
MT-TH	ENST00000387441.1			downstream_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: 0.0071 AC: 436

Gnomad homoplasmic AF: 0.028 AC: 1592 AN: 56419

Gnomad heteroplasmic AF: 0.00011 AC: 6 AN: 56419

Alfa AF: 0.00305 Hom.: 6

Mitomap

DEAF

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Mar 10, 2017

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 19, 2018

- -

Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1

Benign, 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.12236G>A variant in MT-TS2 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.0
Hmtvar	Benign	0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28359170; hg19: chrM-12237; COSMIC: COSV62293881;