6-87514311-CAAAAAAAAA-CAAAAAAA

Variant names:

• chr6-87514311-CAA-C
• rs5878032
• NM_020320.5:c.*100_*101delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001350505.2(RARS2):​c.1723-5_1723-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 562,694 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 0.00058 (0 hom., cov: 0)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: RARS2 NM_001350505.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARS2	NM_020320.5	c.*100_*101delTT		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.*100_*101delTT		3_prime_UTR_variant	Exon 20 of 20	1	NM_020320.5	ENSP00000358549.5

Frequencies

GnomAD3 genomes AF: 0.000571 AC: 64 AN: 112172 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00130

Gnomad ASJ AF: 0.00108

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00353

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000319

Gnomad OTH AF: 0.000680

GnomAD4 exome AF: 0.0415 AC: 18696 AN: 450496 Hom.: 0 AF XY: 0.0417 AC XY: 10109 AN XY: 242200

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.0641

Gnomad4 ASJ exome AF: 0.0472

Gnomad4 EAS exome AF: 0.0388

Gnomad4 SAS exome AF: 0.0470

Gnomad4 FIN exome AF: 0.0389

Gnomad4 NFE exome AF: 0.0398

Gnomad4 OTH exome AF: 0.0400

GnomAD4 genome AF: 0.000579 AC: 65 AN: 112198 Hom.: 0 Cov.: 0 AF XY: 0.000711 AC XY: 38 AN XY: 53426

Gnomad4 AFR AF: 0.000278

Gnomad4 AMR AF: 0.00130

Gnomad4 ASJ AF: 0.00108

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00353

Gnomad4 NFE AF: 0.000319

Gnomad4 OTH AF: 0.000677

ClinVar

Not reported in ClinVar

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;