rs78861628

Positions:

chr20-5302393-G-A

Variant summary

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

The NM_144773.4(PROKR2):c.802C>T(p.Arg268Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,614,202 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 52 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 56 hom. )

Consequence

PROKR2
NM_144773.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 9.42

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00959307).

BP6

Variant 20-5302393-G-A is Benign according to our data. Variant chr20-5302393-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 282345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-5302393-G-A is described in Lovd as [Pathogenic]. Variant chr20-5302393-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2010/152324) while in subpopulation AFR AF= 0.0453 (1885/41568). AF 95% confidence interval is 0.0436. There are 52 homozygotes in gnomad4. There are 969 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 52 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROKR2	NM_144773.4 linkuse as main transcript	c.802C>T	p.Arg268Cys	missense_variant	3/3	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2 linkuse as main transcript	c.802C>T	p.Arg268Cys	missense_variant	3/4		XP_016883135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PROKR2	ENST00000678254.1 linkuse as main transcript	c.802C>T	p.Arg268Cys	missense_variant	3/3		NM_144773.4	ENSP00000504128	P1
PROKR2	ENST00000217270.4 linkuse as main transcript	c.802C>T	p.Arg268Cys	missense_variant	3/3	1		ENSP00000217270	P1
PROKR2	ENST00000678059.1 linkuse as main transcript	c.694C>T	p.Arg232Cys	missense_variant	3/3			ENSP00000503366

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2007

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0454

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00391

AC:

983

AN:

251350

Hom.:

AF XY:

0.00305

AC XY:

415

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0462

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00174

AC:

2540

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1123

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0469

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000434

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.0132

AC:

2010

AN:

152324

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

969

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0453

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.0149

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0422

AC:

186

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00469

AC:

569

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 02, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 15, 2015	- -

Hypogonadotropic hypogonadism 3 with or without anosmia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.59

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.63

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.56

MVP

0.83

ClinPred

0.020

GERP RS

4.1

Varity_R

0.47

gMVP

0.60

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