Variant 1-54757589-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0630

Variant links:

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]

PARS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARS2	NM_152268.4 linkuse as main transcript	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 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.0216

AC XY:

4944

AN XY:

228424

show subpopulations

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.:

Cov.:

AF XY:

0.0179

AC XY:

1331

AN XY:

74398

show subpopulations

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.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.00289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over