2-55236762-C-T

Position:

• chr2-55236762-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002453.3(MTIF2):​c.2070G>A​(p.Met690Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTIF2 NM_002453.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.51

Genes affected

MTIF2 (HGNC:7441): (mitochondrial translational initiation factor 2) During the initiation of protein biosynthesis, initiation factor-2 (IF-2) promotes the binding of the initiator tRNA to the small subunit of the ribosome in a GTP-dependent manner. Prokaryotic IF-2 is a single polypeptide, while eukaryotic cytoplasmic IF-2 (eIF-2) is a trimeric protein. Bovine liver mitochondria contain IF-2(mt), an 85-kD monomeric protein that is equivalent to prokaryotic IF-2. The predicted 727-amino acid human protein contains a 29-amino acid presequence. Human IF-2(mt) shares 32 to 38% amino acid sequence identity with yeast IF-2(mt) and several prokaryotic IF-2s, with the greatest degree of conservation in the G domains of the proteins. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTIF2	NM_002453.3	c.2070G>A	p.Met690Ile	missense_variant	16/16	ENST00000263629.9	NP_002444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTIF2	ENST00000263629.9	c.2070G>A	p.Met690Ile	missense_variant	16/16	1	NM_002453.3	ENSP00000263629	P1
MTIF2	ENST00000394600.7	c.2070G>A	p.Met690Ile	missense_variant	13/13	2		ENSP00000378099	P1
MTIF2	ENST00000403721.5	c.2070G>A	p.Met690Ile	missense_variant	15/15	5		ENSP00000384481	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.2070G>A (p.M690I) alteration is located in exon 17 (coding exon 13) of the MTIF2 gene. This alteration results from a G to A substitution at nucleotide position 2070, causing the methionine (M) at amino acid position 690 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	.;.;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.059	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.70
MutPred		0.38		Loss of ubiquitination at K687 (P = 0.0618);Loss of ubiquitination at K687 (P = 0.0618);Loss of ubiquitination at K687 (P = 0.0618);
MVP		0.54
MPC		0.060
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.40
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr2-55463898;