Genetic Variant RARS2:c.*98_*101delTTTT (chr6-87514311-CAAAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001350505.2(RARS2):c.1723-7_1723-4delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 574,238 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

RARS2
NM_001350505.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.613

Variant links:

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]

RARS2 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
RARS2	NM_020320.5 link	c.98_101delTTTT		3_prime_UTR_variant	Exon 20 of 20	ENST00000369536.10	NP_064716.2	Q5T160

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARS2	ENST00000369536 link	c.98_101delTTTT		3_prime_UTR_variant	Exon 20 of 20	1	NM_020320.5	ENSP00000358549.5		Q5T160

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000870

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000357

AC:

165

AN:

462038

Hom.:

AF XY:

0.000342

AC XY:

AN XY:

248510

show subpopulations

Gnomad4 AFR exome

AF:

0.000474

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.000312

Gnomad4 EAS exome

AF:

0.000352

Gnomad4 SAS exome

AF:

0.000260

Gnomad4 FIN exome

AF:

0.000178

Gnomad4 NFE exome

AF:

0.000374

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.0000357

AC:

AN:

112200

Hom.:

Cov.:

AF XY:

0.0000375

AC XY:

AN XY:

53388

show subpopulations

Gnomad4 AFR

AF:

0.000104

Gnomad4 AMR

AF:

0.0000870

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

6-87514311-CAAAAAAAAA-CAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over