1-54757589-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152268.4(PARS2):c.*145A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 589,370 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (35 hom., cov: 32)
  • Exomes 𝑓: 0.022 (145 hom.)
• Consequence: PARS2 NM_152268.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0630

Genes affected

PARS2 (HGNC:30563): (prolyl-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 proline to tRNA molecules. Mutations have been found in this gene in some patients with Alpers syndrome. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-54757589-T-C is Benign according to our data. Variant chr1-54757589-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1201465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0186 (2824/152164) while in subpopulation NFE AF= 0.0297 (2018/68002). AF 95% confidence interval is 0.0286. There are 35 homozygotes in gnomad4. There are 1331 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARS2	NM_152268.4	c.*145A>G		3_prime_UTR_variant	2/2	ENST00000371279.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARS2	ENST00000371279.4	c.*145A>G		3_prime_UTR_variant	2/2	1	NM_152268.4	P1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2824 AN: 152046 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00602

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0223 AC: 9767 AN: 437206 Hom.: 145 Cov.: 5 AF XY: 0.0216 AC XY: 4944 AN XY: 228424

Gnomad4 AFR exome AF: 0.00489

Gnomad4 AMR exome AF: 0.00863

Gnomad4 ASJ exome AF: 0.00835

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00846

Gnomad4 FIN exome AF: 0.0266

Gnomad4 NFE exome AF: 0.0291

Gnomad4 OTH exome AF: 0.0212

GnomAD4 genome AF: 0.0186 AC: 2824 AN: 152164 Hom.: 35 Cov.: 32 AF XY: 0.0179 AC XY: 1331 AN XY: 74398

Gnomad4 AFR AF: 0.00600

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00808

Gnomad4 FIN AF: 0.0257

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0238 Hom.: 13

Bravo AF: 0.0167

Asia WGS AF: 0.00289 AC: 11 AN: 3476

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.6
Dann	Benign	0.46

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: rs112294032; hg19: chr1-55223262;