6-87514172-G-A

Position:

• chr6-87514172-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020320.5(RARS2):​c.*241C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 152,050 control chromosomes in the GnomAD database, including 664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.090 (664 hom., cov: 31)
• Consequence: RARS2 NM_020320.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.252

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 6-87514172-G-A is Benign according to our data. Variant chr6-87514172-G-A is described in ClinVar as [Benign]. Clinvar id is 1260098.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARS2	NM_020320.5	c.*241C>T		3_prime_UTR_variant	20/20	ENST00000369536.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARS2	ENST00000369536.10	c.*241C>T		3_prime_UTR_variant	20/20	1	NM_020320.5	P1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13735 AN: 151932 Hom.: 658 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.0908

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0848

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0905 AC: 13760 AN: 152050 Hom.: 664 Cov.: 31 AF XY: 0.0913 AC XY: 6787 AN XY: 74328

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0714

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.0957

Gnomad4 SAS AF: 0.0899

Gnomad4 FIN AF: 0.0945

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.0786 Hom.: 58

Bravo AF: 0.0891

Asia WGS AF: 0.135 AC: 469 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

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35706399; hg19: chr6-88223890;