chr1-54757517-C-T

Position:

• chr1-54757517-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152268.4(PARS2):​c.*217G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 504,458 control chromosomes in the GnomAD database, including 14,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3957 hom., cov: 32)
  • Exomes 𝑓: 0.22 (10424 hom.)
• Consequence: PARS2 NM_152268.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-54757517-C-T is Benign according to our data. Variant chr1-54757517-C-T is described in ClinVar as [Benign]. Clinvar id is 1265293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARS2	NM_152268.4	c.*217G>A		3_prime_UTR_variant	2/2	ENST00000371279.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARS2	ENST00000371279.4	c.*217G>A		3_prime_UTR_variant	2/2	1	NM_152268.4	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32008 AN: 152006 Hom.: 3950 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.217 AC: 76313 AN: 352334 Hom.: 10424 Cov.: 3 AF XY: 0.217 AC XY: 39830 AN XY: 183426

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.544

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.211 AC: 32041 AN: 152124 Hom.: 3957 Cov.: 32 AF XY: 0.215 AC XY: 16004 AN XY: 74370

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.208

Alfa AF: 0.197 Hom.: 2442

Bravo AF: 0.228

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2240396; hg19: chr1-55223190;