rs569593326

Variant names:

• chr13-110705860-C-A
• rs569593326
• NM_024537.4:c.224+10G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-110705860-C-A
• chr13-110705860-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_024537.4(CARS2):​c.224+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,550,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CARS2 NM_024537.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.88
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 27

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, G2P
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 13-110705860-C-A is Benign according to our data. Variant chr13-110705860-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 475626.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS2	NM_024537.4	c.224+10G>T		intron_variant	Intron 1 of 14	ENST00000257347.9	NP_078813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARS2	ENST00000257347.9	c.224+10G>T		intron_variant	Intron 1 of 14	1	NM_024537.4	ENSP00000257347.4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152036 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000393 AC: 6 AN: 152618 AF XY: 0.0000362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000421

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000235

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1397880 Hom.: 0 Cov.: 31 AF XY: 0.00000579 AC XY: 4 AN XY: 690678

African (AFR) AF: 0.00 AC: 0 AN: 31892

American (AMR) AF: 0.00 AC: 0 AN: 37106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24734

East Asian (EAS) AF: 0.000138 AC: 5 AN: 36324

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082098

Other (OTH) AF: 0.0000172 AC: 1 AN: 58054

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41536

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000777 AC: 4 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined oxidative phosphorylation defect type 27 Benign:1

Jan 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.5
DANN	Benign	0.40
PhyloP100		-1.9
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs569593326; hg19: chr13-111358207;