rs8802

Variant names:

• chr6-87514446-T-A
• rs8802
• NM_020320.5:c.1704A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-87514446-T-A
• chr6-87514446-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_020320.5(RARS2):​c.1704A>T​(p.Lys568Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K568K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RARS2 NM_020320.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.859

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 Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a modified_residue N6-acetyllysine (size 0) in uniprot entity SYRM_HUMAN
• 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	c.1704A>T	p.Lys568Asn	missense_variant	Exon 20 of 20	ENST00000369536.10	NP_064716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARS2	ENST00000369536.10	c.1704A>T	p.Lys568Asn	missense_variant	Exon 20 of 20	1	NM_020320.5	ENSP00000358549.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.29
Sift	Benign	0.043	D
Sift4G	Benign	0.14	T
Polyphen		0.078	B
Vest4		0.46
MutPred		0.49		Loss of MoRF binding (P = 0.0262);
MVP		0.76
MPC		0.30
ClinPred		0.90	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8802; hg19: chr6-88224164;