6-87514311-C-CA

Variant names:

• chr6-87514311-C-CA
• rs5878032
• NM_020320.5:c.*101dupT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001350505.2(RARS2):​c.1723-4dupT variant causes a splice region, intron 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_001350505.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter 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 -10 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_single_submitter, 1 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 rank	MANE	Protein	UniProt
RARS2	NM_020320.5	c.*101dupT		3_prime_UTR_variant	Exon 20 of 20	ENST00000369536.10	NP_064716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARS2	ENST00000369536	c.*101dupT		3_prime_UTR_variant	Exon 20 of 20	1	NM_020320.5	ENSP00000358549.5

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, single submitter

Submissions by phenotype

RARS2-related disorder Benign:1

Mar 28, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Aug 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;