2-197705380-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_138395.4(MARS2):c.-26T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,557,322 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (5 hom.)
• Consequence: MARS2 NM_138395.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66

Genes affected

MARS2 (HGNC:25133): (methionyl-tRNA synthetase 2, mitochondrial) This gene produces a mitochondrial methionyl-tRNA synthetase protein that is encoded by the nuclear genome and imported to the mitochondrion. This protein likely functions as a monomer and is predicted to localize to the mitochondrial matrix. Mutations in this gene are associated with the autosomal recessive neurodegenerative disease spastic ataxia-3 (SPAX3). [provided by RefSeq, Apr 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-197705380-T-G is Benign according to our data. Variant chr2-197705380-T-G is described in ClinVar as [Benign]. Clinvar id is 1286037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00553 (842/152290) while in subpopulation AFR AF= 0.0184 (766/41550). AF 95% confidence interval is 0.0174. There are 5 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARS2	NM_138395.4	c.-26T>G		5_prime_UTR_variant	1/1	ENST00000282276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARS2	ENST00000282276.8	c.-26T>G		5_prime_UTR_variant	1/1		NM_138395.4	P1
	ENST00000409845.1	n.166+6516T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 837 AN: 152172 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00167 AC: 350 AN: 209462 Hom.: 0 AF XY: 0.00128 AC XY: 147 AN XY: 114864

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.000911

Gnomad ASJ exome AF: 0.00306

Gnomad EAS exome AF: 0.000235

Gnomad SAS exome AF: 0.000161

Gnomad FIN exome AF: 0.000207

Gnomad NFE exome AF: 0.000347

Gnomad OTH exome AF: 0.000811

GnomAD4 exome AF: 0.000828 AC: 1164 AN: 1405032 Hom.: 5 Cov.: 30 AF XY: 0.000730 AC XY: 506 AN XY: 693034

Gnomad4 AFR exome AF: 0.0187

Gnomad4 AMR exome AF: 0.00118

Gnomad4 ASJ exome AF: 0.00350

Gnomad4 EAS exome AF: 0.000181

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.000197

Gnomad4 NFE exome AF: 0.000279

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00553 AC: 842 AN: 152290 Hom.: 5 Cov.: 33 AF XY: 0.00543 AC XY: 404 AN XY: 74470

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00144 Hom.: 1

Bravo AF: 0.00642

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	3.3
Dann	Benign	0.30

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

LitVar

Other links and lift over

dbSNP: rs202121719; hg19: chr2-198570104;