rs4275650

Variant names:

• chr11-78573777-T-A
• rs4275650
• NM_024678.6:c.141+571A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-78573777-T-A
• chr11-78573777-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024678.6(NARS2):​c.141+571A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,072 control chromosomes in the GnomAD database, including 39,185 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 0.71 (39185 hom., cov: 33)
• Consequence: NARS2 NM_024678.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 5 publications found

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]

NARS2 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 24

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: Illumina
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive 94

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NARS2	NM_024678.6	c.141+571A>T		intron_variant	Intron 1 of 13	ENST00000281038.10	NP_078954.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NARS2	ENST00000281038.10	c.141+571A>T		intron_variant	Intron 1 of 13	1	NM_024678.6	ENSP00000281038.5

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108301 AN: 151954 Hom.: 39172 Cov.: 33

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.713 AC: 108357 AN: 152072 Hom.: 39185 Cov.: 33 AF XY: 0.706 AC XY: 52498 AN XY: 74312

African (AFR) AF: 0.622 AC: 25808 AN: 41460

American (AMR) AF: 0.669 AC: 10226 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2338 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2964 AN: 5166

South Asian (SAS) AF: 0.723 AC: 3486 AN: 4820

European-Finnish (FIN) AF: 0.677 AC: 7151 AN: 10568

Middle Eastern (MID) AF: 0.669 AC: 194 AN: 290

European-Non Finnish (NFE) AF: 0.793 AC: 53950 AN: 67990

Other (OTH) AF: 0.717 AC: 1515 AN: 2112

Alfa AF: 0.695 Hom.: 2427

Bravo AF: 0.703

Asia WGS AF: 0.684 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.5
DANN	Benign	0.68
PhyloP100		1.3
PromoterAI		0.0070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs4275650; hg19: chr11-78284822;