Variant 13-110641500-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_StrongBA1

The NM_024537.4(CARS2):c.*37C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,524,314 control chromosomes in the GnomAD database, including 21,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5849 hom., cov: 33)

Exomes 𝑓: 0.14 ( 16144 hom. )

Consequence

CARS2
NM_024537.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.428

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:

CARS2 (HGNC:):

CARS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 13-110641500-G-A is Benign according to our data. Variant chr13-110641500-G-A is described in ClinVar as [Benign]. Clinvar id is 1291054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARS2	NM_024537.4 linkuse as main transcript	c.*37C>T		3_prime_UTR_variant	15/15	ENST00000257347.9	NP_078813.1	Q9HA77B7Z7E6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARS2	ENST00000257347 linkuse as main transcript	c.*37C>T		3_prime_UTR_variant	15/15	1	NM_024537.4	ENSP00000257347.4		Q9HA77

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35264

AN:

152062

Hom.:

5822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.178

AC:

44764

AN:

251200

Hom.:

5197

AF XY:

0.170

AC XY:

23091

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.160

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.138

AC:

188968

AN:

1372134

Hom.:

16144

Cov.:

AF XY:

0.138

AC XY:

95016

AN XY:

687728

show subpopulations

Gnomad4 AFR exome

AF:

0.483

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.232

AC:

35362

AN:

152180

Hom.:

5849

Cov.:

AF XY:

0.231

AC XY:

17159

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.466

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.148

Hom.:

2277

Bravo

AF:

0.250

Asia WGS

AF:

0.201

AC:

697

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 37% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.1

DANN

Benign

0.63

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