6-87514311-C-CA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020320.5(RARS2):c.*101_*102insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 566,554 control chromosomes in the GnomAD database, including 464 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (442 hom., cov: 0)
  • Exomes 𝑓: 0.13 (22 hom.)
• Consequence: RARS2 NM_020320.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.613

Genes affected

RARS2 (HGNC:21406): (arginyl-tRNA synthetase 2, mitochondrial) This nuclear gene encodes a protein that localizes to the mitochondria, where it catalyzes the transfer of L-arginine to its cognate tRNA, an important step in translation of mitochondrially-encoded proteins. Defects in this gene are a cause of pontocerebellar hypoplasia type 6 (PCH6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 6-87514311-C-CA is Benign according to our data. Variant chr6-87514311-C-CA is described in ClinVar as [Benign]. Clinvar id is 1221069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARS2	NM_020320.5	c.*101_*102insT		3_prime_UTR_variant	20/20	ENST00000369536.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARS2	ENST00000369536.10	c.*101_*102insT		3_prime_UTR_variant	20/20	1	NM_020320.5	P1

Frequencies

GnomAD3 genomes AF: 0.0952 AC: 10671 AN: 112042 Hom.: 439 Cov.: 0

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0531

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0593

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0966

GnomAD4 exome AF: 0.130 AC: 58892 AN: 454480 Hom.: 22 AF XY: 0.129 AC XY: 31590 AN XY: 244210

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0894

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.0953 AC: 10679 AN: 112074 Hom.: 442 Cov.: 0 AF XY: 0.0953 AC XY: 5088 AN XY: 53382

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0937

Gnomad4 OTH AF: 0.104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

RARS2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5878032; hg19: chr6-88224029;