11-78436529-A-AT

Position:

• chr11-78436529-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_024678.6(NARS2):​c.*140_*141insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,044,866 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (3 hom.)
• Consequence: NARS2 NM_024678.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.397

Genes affected

NARS2 (HGNC:26274): (asparaginyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class II 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 asparagine to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 24 (COXPD24). [provided by RefSeq, Mar 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-78436529-A-AT is Benign according to our data. Variant chr11-78436529-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 1204738.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00541 (824/152266) while in subpopulation AFR AF= 0.019 (791/41542). AF 95% confidence interval is 0.0179. There are 13 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NARS2	NM_024678.6	c.*140_*141insA		3_prime_UTR_variant	14/14	ENST00000281038.10
NARS2	NM_001243251.2	c.*140_*141insA		3_prime_UTR_variant	14/14
NARS2	XM_011545253.3	c.*140_*141insA		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NARS2	ENST00000281038.10	c.*140_*141insA		3_prime_UTR_variant	14/14	1	NM_024678.6	P1
	ENST00000534168.1	n.36-7113dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00542 AC: 824 AN: 152148 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.000527 AC: 470 AN: 892600 Hom.: 3 Cov.: 12 AF XY: 0.000427 AC XY: 192 AN XY: 449216

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.000461

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000208

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000257

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.00541 AC: 824 AN: 152266 Hom.: 13 Cov.: 32 AF XY: 0.00496 AC XY: 369 AN XY: 74448

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00470 Hom.: 1

Bravo AF: 0.00629

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

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs151249725; hg19: chr11-78147575;