Variant 13-110645957-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024537.4(CARS2):c.1317+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 1,610,366 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 63 hom. )

Consequence

CARS2
NM_024537.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.365

Variant links:

Genes affected

CARS2 (HGNC:25695): (cysteinyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of cysteine to tRNA molecules. A splice-site mutation in this gene has been associated with a novel progressive myoclonic epilepsy disease with similar symptoms to MERRF syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

CARS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 13-110645957-G-A is Benign according to our data. Variant chr13-110645957-G-A is described in ClinVar as [Benign]. Clinvar id is 382608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00585 (891/152316) while in subpopulation SAS AF= 0.0108 (52/4832). AF 95% confidence interval is 0.00843. There are 6 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARS2	NM_024537.4 linkuse as main transcript	c.1317+10C>T		intron_variant		ENST00000257347.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARS2	ENST00000257347.9 linkuse as main transcript	c.1317+10C>T		intron_variant		1	NM_024537.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

893

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00767

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00747

AC:

1842

AN:

246726

Hom.:

AF XY:

0.00806

AC XY:

1076

AN XY:

133460

show subpopulations

Gnomad AFR exome

AF:

0.00100

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.0307

Gnomad EAS exome

AF:

0.000500

Gnomad SAS exome

AF:

0.0129

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00831

Gnomad OTH exome

AF:

0.00820

GnomAD4 exome

AF:

0.00719

AC:

10479

AN:

1458050

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

5453

AN XY:

725350

show subpopulations

Gnomad4 AFR exome

AF:

0.000813

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.0311

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.00187

Gnomad4 NFE exome

AF:

0.00699

Gnomad4 OTH exome

AF:

0.00860

GnomAD4 genome

AF:

0.00585

AC:

891

AN:

152316

Hom.:

Cov.:

AF XY:

0.00571

AC XY:

425

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00767

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00808

Hom.:

Bravo

AF:

0.00628

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Combined oxidative phosphorylation defect type 27

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.4

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over