chr1-220115616-A-C

Position:

• chr1-220115616-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366922.3(IARS2):​c.1640+1142A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,100 control chromosomes in the GnomAD database, including 1,506 homozygotes. 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: 𝑓 0.13 (1506 hom., cov: 33)
• Consequence: IARS2 ENST00000366922.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IARS2	NM_018060.4	c.1640+1142A>C		intron_variant		ENST00000366922.3	NP_060530.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IARS2	ENST00000366922.3	c.1640+1142A>C		intron_variant		1	NM_018060.4	ENSP00000355889	P1
IARS2	ENST00000490891.1	n.24+1142A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19726 AN: 151982 Hom.: 1495 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19774 AN: 152100 Hom.: 1506 Cov.: 33 AF XY: 0.129 AC XY: 9558 AN XY: 74370

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0856

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.132

Alfa AF: 0.135 Hom.: 241

Bravo AF: 0.128

Asia WGS AF: 0.164 AC: 569 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.40

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: rs17007135; hg19: chr1-220288958;