rs149447502

Positions:

• chr12-32755771-G-A
• chr12-32755771-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040436.3(YARS2):​c.104C>T​(p.Ala35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A35D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: YARS2 NM_001040436.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08709854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YARS2	NM_001040436.3	c.104C>T	p.Ala35Val	missense_variant	1/5	ENST00000324868.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YARS2	ENST00000324868.13	c.104C>T	p.Ala35Val	missense_variant	1/5	1	NM_001040436.3	P1
	ENST00000666291.1	n.262G>A		non_coding_transcript_exon_variant	1/1
YARS2	ENST00000548490.1	c.26C>T	p.Ala9Val	missense_variant, NMD_transcript_variant	1/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250920 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.078
Sift	Benign	0.033	D
Sift4G	Benign	0.21	T
Polyphen		0.047	B
Vest4		0.21
MutPred		0.35		Gain of helix (P = 0.0325);
MVP		0.38
MPC		0.47
ClinPred		0.062	T
GERP RS		0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.034
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: rs149447502; hg19: chr12-32908705;