rs777716260

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018060.4(IARS2):​c.16C>A​(p.Arg6Ser) 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. 13/20 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. R6C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

IARS2
NM_018060.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.482
Variant links:
Genes affected
IARS2 (HGNC:29685): (isoleucyl-tRNA synthetase 2, mitochondrial) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Two forms of isoleucine-tRNA synthetase exist, a cytoplasmic form and a mitochondrial form. This gene encodes the mitochondrial isoleucine-tRNA synthetase which belongs to the class-I aminoacyl-tRNA synthetase family. [provided by RefSeq, Dec 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.06807345).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IARS2NM_018060.4 linkc.16C>A p.Arg6Ser missense_variant Exon 1 of 23 ENST00000366922.3 NP_060530.3 Q9NSE4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IARS2ENST00000366922.3 linkc.16C>A p.Arg6Ser missense_variant Exon 1 of 23 1 NM_018060.4 ENSP00000355889.2 Q9NSE4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000851
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
13
DANN
Benign
0.79
DEOGEN2
Benign
0.020
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.068
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.62
N
Sift
Benign
0.13
T
Sift4G
Benign
0.71
T
Polyphen
0.0010
B
Vest4
0.17
MutPred
0.24
Gain of phosphorylation at R6 (P = 0.0223);
MVP
0.18
ClinPred
0.057
T
GERP RS
-5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.14
gMVP
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777716260; hg19: chr1-220267574; API