12-32747335-T-G

Position:

• chr12-32747335-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040436.3(YARS2):​c.1303A>C​(p.Ser435Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: YARS2 NM_001040436.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

Genes affected

YARS2 (HGNC:24249): (tyrosyl-tRNA synthetase 2) This gene encodes a mitochondrial protein that catalyzes the attachment of tyrosine to tRNA(Tyr). Mutations in this gene are associated with myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2). [provided by RefSeq, Jan 2011]

YARS2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3867936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YARS2	NM_001040436.3	c.1303A>C	p.Ser435Arg	missense_variant	5/5	ENST00000324868.13	NP_001035526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YARS2	ENST00000324868.13	c.1303A>C	p.Ser435Arg	missense_variant	5/5	1	NM_001040436.3	ENSP00000320658.8
YARS2	ENST00000548490.1	n.*314A>C		non_coding_transcript_exon_variant	5/5	5		ENSP00000447710.1
YARS2	ENST00000551673.5	n.200A>C		non_coding_transcript_exon_variant	2/3	5
YARS2	ENST00000548490.1	n.*314A>C		3_prime_UTR_variant	5/5	5		ENSP00000447710.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.047
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.34
Sift	Benign	0.31	T
Sift4G	Benign	0.30	T
Polyphen		0.21	B
Vest4		0.54
MutPred		0.47		Gain of methylation at S435 (P = 0.0136);
MVP		0.65
MPC		0.54
ClinPred		0.46	T
GERP RS		5.7
Varity_R		0.097
gMVP		0.51

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: rs587777215; hg19: chr12-32900269;