rs3746684

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144773.4(PROKR2):c.465C>T(p.Leu155Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,610,316 control chromosomes in the GnomAD database, including 126,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12642 hom., cov: 33)

Exomes 𝑓: 0.39 ( 113595 hom. )

Consequence

PROKR2
NM_144773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.462

Variant links:

Genes affected

PROKR2 (HGNC:15836): (prokineticin receptor 2) Prokineticins are secreted proteins that can promote angiogenesis and induce strong gastrointestinal smooth muscle contraction. The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor for prokineticins. The encoded protein is similar in sequence to GPR73, another G protein-coupled receptor for prokineticins. [provided by RefSeq, Jul 2008]

PROKR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 20-5302730-G-A is Benign according to our data. Variant chr20-5302730-G-A is described in ClinVar as [Benign]. Clinvar id is 338859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-5302730-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.462 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROKR2	NM_144773.4 link	c.465C>T	p.Leu155Leu	synonymous_variant	Exon 3 of 3	ENST00000678254.1	NP_658986.1	Q8NFJ6A8K1T0
PROKR2	XM_017027646.2 link	c.465C>T	p.Leu155Leu	synonymous_variant	Exon 3 of 4		XP_016883135.1	Q8NFJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PROKR2	ENST00000678254.1 link	c.465C>T	p.Leu155Leu	synonymous_variant	Exon 3 of 3		NM_144773.4	ENSP00000504128.1	Q8NFJ6
PROKR2	ENST00000217270.4 link	c.465C>T	p.Leu155Leu	synonymous_variant	Exon 3 of 3	1		ENSP00000217270.3	Q8NFJ6
PROKR2	ENST00000678059.1 link	c.357C>T	p.Leu119Leu	synonymous_variant	Exon 3 of 3			ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61714

AN:

151936

Hom.:

12622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.397

AC:

99358

AN:

250164

Hom.:

20167

AF XY:

0.398

AC XY:

53885

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.392

AC:

572274

AN:

1458262

Hom.:

113595

Cov.:

AF XY:

0.393

AC XY:

285267

AN XY:

725548

show subpopulations

Gnomad4 AFR exome

AF:

0.447

Gnomad4 AMR exome

AF:

0.394

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.433

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.393

GnomAD4 genome

AF:

0.406

AC:

61758

AN:

152054

Hom.:

12642

Cov.:

AF XY:

0.406

AC XY:

30188

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.452

Gnomad4 AMR

AF:

0.402

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.397

Alfa

AF:

0.386

Hom.:

13334

Bravo

AF:

0.412

Asia WGS

AF:

0.422

AC:

1464

AN:

3478

EpiCase

AF:

0.382

EpiControl

AF:

0.373

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypogonadotropic hypogonadism 3 with or without anosmia

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 27, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.059

DANN

Benign

0.56

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