20-5302610-C-G

Position:

chr20-5302610-C-G

Variant summary

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

The NM_144773.4(PROKR2):c.585G>C(p.Thr195=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,613,922 control chromosomes in the GnomAD database, including 453,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40975 hom., cov: 32)

Exomes 𝑓: 0.75 ( 412053 hom. )

Consequence

PROKR2
NM_144773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.51

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=-0.89).

BP6

Variant 20-5302610-C-G is Benign according to our data. Variant chr20-5302610-C-G is described in ClinVar as [Benign]. Clinvar id is 338858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-5302610-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROKR2	NM_144773.4 linkuse as main transcript	c.585G>C	p.Thr195=	synonymous_variant	3/3	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2 linkuse as main transcript	c.585G>C	p.Thr195=	synonymous_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.585G>C	p.Thr195=	synonymous_variant	3/3		NM_144773.4	ENSP00000504128	P1
PROKR2	ENST00000217270.4 linkuse as main transcript	c.585G>C	p.Thr195=	synonymous_variant	3/3	1		ENSP00000217270	P1
PROKR2	ENST00000678059.1 linkuse as main transcript	c.477G>C	p.Thr159=	synonymous_variant	3/3			ENSP00000503366

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111570

AN:

152002

Hom.:

40921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.703

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.772

Gnomad FIN

AF:

0.772

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.747

Gnomad OTH

AF:

0.739

GnomAD3 exomes

AF:

0.746

AC:

187657

AN:

251476

Hom.:

70228

AF XY:

0.750

AC XY:

101993

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.704

Gnomad AMR exome

AF:

0.749

Gnomad ASJ exome

AF:

0.788

Gnomad EAS exome

AF:

0.679

Gnomad SAS exome

AF:

0.770

Gnomad FIN exome

AF:

0.769

Gnomad NFE exome

AF:

0.748

Gnomad OTH exome

AF:

0.739

GnomAD4 exome

AF:

0.750

AC:

1096444

AN:

1461802

Hom.:

412053

Cov.:

AF XY:

0.751

AC XY:

546485

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.697

Gnomad4 AMR exome

AF:

0.746

Gnomad4 ASJ exome

AF:

0.792

Gnomad4 EAS exome

AF:

0.636

Gnomad4 SAS exome

AF:

0.772

Gnomad4 FIN exome

AF:

0.761

Gnomad4 NFE exome

AF:

0.753

Gnomad4 OTH exome

AF:

0.748

GnomAD4 genome

AF:

0.734

AC:

111677

AN:

152120

Hom.:

40975

Cov.:

AF XY:

0.736

AC XY:

54701

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.704

Gnomad4 AMR

AF:

0.733

Gnomad4 ASJ

AF:

0.796

Gnomad4 EAS

AF:

0.678

Gnomad4 SAS

AF:

0.771

Gnomad4 FIN

AF:

0.772

Gnomad4 NFE

AF:

0.747

Gnomad4 OTH

AF:

0.740

Alfa

AF:

0.733

Hom.:

10479

Bravo

AF:

0.730

Asia WGS

AF:

0.698

AC:

2427

AN:

3478

EpiCase

AF:

0.762

EpiControl

AF:

0.751

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypogonadotropic hypogonadism 3 with or without anosmia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 27, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.33

DANN

Benign

0.64

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