NM_020320.5:c.*93_*101delTTTTTTTTT

Variant names:

• chr6-87514311-CAAAAAAAAA-C
• rs5878032
• NM_020320.5:c.*93_*101delTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020320.5(RARS2):​c.*93_*101delTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 462,584 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: RARS2 NM_020320.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.613
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• pontocerebellar hypoplasia type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Laboratory for Molecular Medicine, Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020320.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARS2	NM_020320.5	MANE Select	c.*93_*101delTTTTTTTTT		3_prime_UTR	Exon 20 of 20	NP_064716.2	Q5T160
	RARS2	NM_001318785.2		c.*93_*101delTTTTTTTTT		3_prime_UTR	Exon 19 of 19	NP_001305714.1	H0UI22
	RARS2	NM_001350507.2		c.*93_*101delTTTTTTTTT		3_prime_UTR	Exon 21 of 21	NP_001337436.1	H0UI22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARS2	ENST00000369536.10	TSL:1 MANE Select	c.*93_*101delTTTTTTTTT		3_prime_UTR	Exon 20 of 20	ENSP00000358549.5	Q5T160
	RARS2	ENST00000685408.1		c.*93_*101delTTTTTTTTT		3_prime_UTR	Exon 21 of 21	ENSP00000509026.1	H0UI22
	RARS2	ENST00000689174.1		c.*93_*101delTTTTTTTTT		3_prime_UTR	Exon 20 of 20	ENSP00000510542.1	H0UI22

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000432 AC: 2 AN: 462584 Hom.: 0 AF XY: 0.00000402 AC XY: 1 AN XY: 248808

African (AFR) AF: 0.00 AC: 0 AN: 10556

American (AMR) AF: 0.00 AC: 0 AN: 18506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12848

East Asian (EAS) AF: 0.00 AC: 0 AN: 19898

South Asian (SAS) AF: 0.00 AC: 0 AN: 49980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1548

European-Non Finnish (NFE) AF: 0.00000667 AC: 2 AN: 299800

Other (OTH) AF: 0.00 AC: 0 AN: 21376

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61

Splicing

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

Other links and lift over

dbSNP: rs5878032; hg19: chr6-88224029;