rs3746683

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.525C>G(p.Ala175Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,614,038 control chromosomes in the GnomAD database, including 11,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A175A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.12 ( 1111 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10819 hom. )

Consequence

PROKR2
NM_144773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.96

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=-0.88).

BP6

Variant 20-5302670-G-C is Benign according to our data. Variant chr20-5302670-G-C is described in ClinVar as [Benign]. Clinvar id is 138812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-5302670-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROKR2	NM_144773.4 link	c.525C>G	p.Ala175Ala	synonymous_variant	Exon 3 of 3	ENST00000678254.1	NP_658986.1	Q8NFJ6A8K1T0
PROKR2	XM_017027646.2 link	c.525C>G	p.Ala175Ala	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.525C>G	p.Ala175Ala	synonymous_variant	Exon 3 of 3		NM_144773.4	ENSP00000504128.1	Q8NFJ6
PROKR2	ENST00000217270.4 link	c.525C>G	p.Ala175Ala	synonymous_variant	Exon 3 of 3	1		ENSP00000217270.3	Q8NFJ6
PROKR2	ENST00000678059.1 link	c.417C>G	p.Ala139Ala	synonymous_variant	Exon 3 of 3			ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17748

AN:

152148

Hom.:

1097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0807

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0352

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.113

AC:

28316

AN:

251430

Hom.:

1847

AF XY:

0.115

AC XY:

15692

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0591

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0322

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.118

AC:

173089

AN:

1461772

Hom.:

10819

Cov.:

AF XY:

0.119

AC XY:

86546

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.0606

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.0395

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.117

AC:

17788

AN:

152266

Hom.:

1111

Cov.:

AF XY:

0.119

AC XY:

8853

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.0805

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.0353

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0935

Hom.:

260

Bravo

AF:

0.109

Asia WGS

AF:

0.0890

AC:

310

AN:

3478

EpiCase

AF:

0.127

EpiControl

AF:

0.122

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 06, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Jan 30, 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:2

Jun 27, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.60

DANN

Benign

0.50

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