chr1-54757524-G-A

Position:

• chr1-54757524-G-A

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.*210C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 524,580 control chromosomes in the GnomAD database, including 652 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 (108 hom., cov: 32)
  • Exomes 𝑓: 0.021 (544 hom.)
• Consequence: PARS2 NM_152268.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.620

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=-0.84).
• BP6: Variant 1-54757524-G-A is Benign according to our data. Variant chr1-54757524-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARS2	NM_152268.4	c.*210C>T		3_prime_UTR_variant	2/2	ENST00000371279.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARS2	ENST00000371279.4	c.*210C>T		3_prime_UTR_variant	2/2	1	NM_152268.4	P1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2954 AN: 152160 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0212 AC: 7875 AN: 372302 Hom.: 544 Cov.: 3 AF XY: 0.0246 AC XY: 4783 AN XY: 194068

Gnomad4 AFR exome AF: 0.0387

Gnomad4 AMR exome AF: 0.00255

Gnomad4 ASJ exome AF: 0.00221

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0000393

Gnomad4 NFE exome AF: 0.000253

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0194 AC: 2960 AN: 152278 Hom.: 108 Cov.: 32 AF XY: 0.0210 AC XY: 1567 AN XY: 74454

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00648 Hom.: 1

Bravo AF: 0.0174

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.32
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: rs74946945; hg19: chr1-55223197;