6-87514311-CAAAAAAAAA-CAAAAAA

Variant names:

• chr6-87514311-CAAA-C
• rs5878032
• NM_020320.5:c.*99_*101delTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001350505.2(RARS2):​c.1723-6_1723-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 571,850 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 0.0025 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0031 (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0025 (280/112220) while in subpopulation AFR AF= 0.00934 (269/28806). AF 95% confidence interval is 0.00842. There are 0 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARS2	NM_020320.5	c.*99_*101delTTT		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.*99_*101delTTT		3_prime_UTR_variant	Exon 20 of 20	1	NM_020320.5	ENSP00000358549.5

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 280 AN: 112190 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00936

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000609

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: 0.0000375

Gnomad OTH AF: 0.00136

GnomAD4 exome AF: 0.00309 AC: 1422 AN: 459630 Hom.: 0 AF XY: 0.00299 AC XY: 738 AN XY: 247212

Gnomad4 AFR exome AF: 0.00762

Gnomad4 AMR exome AF: 0.00463

Gnomad4 ASJ exome AF: 0.00376

Gnomad4 EAS exome AF: 0.00339

Gnomad4 SAS exome AF: 0.00242

Gnomad4 FIN exome AF: 0.00276

Gnomad4 NFE exome AF: 0.00291

Gnomad4 OTH exome AF: 0.00334

GnomAD4 genome AF: 0.00250 AC: 280 AN: 112220 Hom.: 0 Cov.: 0 AF XY: 0.00251 AC XY: 134 AN XY: 53438

Gnomad4 AFR AF: 0.00934

Gnomad4 AMR AF: 0.000608

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000375

Gnomad4 OTH AF: 0.00136

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;