chr20-5302610-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144773.4(PROKR2):c.585G>C(p.Thr195Thr) 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

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 3 with or without anosmia
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
septooptic dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PROKR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 338858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PROKR2	NM_144773.4 link	c.585G>C	p.Thr195Thr	synonymous_variant	Exon 3 of 3	ENST00000678254.1	NP_658986.1	Q8NFJ6A8K1T0
PROKR2	XM_017027646.2 link	c.585G>C	p.Thr195Thr	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.585G>C	p.Thr195Thr	synonymous_variant	Exon 3 of 3		NM_144773.4	ENSP00000504128.1	Q8NFJ6
PROKR2	ENST00000217270.4 link	c.585G>C	p.Thr195Thr	synonymous_variant	Exon 3 of 3	1		ENSP00000217270.3	Q8NFJ6
PROKR2	ENST00000678059.1 link	c.477G>C	p.Thr159Thr	synonymous_variant	Exon 3 of 3			ENSP00000503366.1	A0A7I2V3D2

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

GnomAD2 exomes

AF:

0.746

AC:

187657

AN:

251476

AF XY:

0.750

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 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

African (AFR)

AF:

0.697

AC:

23319

AN:

33480

American (AMR)

AF:

0.746

AC:

33367

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.792

AC:

20698

AN:

26136

East Asian (EAS)

AF:

0.636

AC:

25241

AN:

39700

South Asian (SAS)

AF:

0.772

AC:

66551

AN:

86254

European-Finnish (FIN)

AF:

0.761

AC:

40630

AN:

53416

Middle Eastern (MID)

AF:

0.801

AC:

4620

AN:

5768

European-Non Finnish (NFE)

AF:

0.753

AC:

836830

AN:

1111928

Other (OTH)

AF:

0.748

AC:

45188

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17988

35975

53963

71950

89938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20346

40692

61038

81384

101730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.734

AC:

111677

AN:

152120

Hom.:

40975

Cov.:

AF XY:

0.736

AC XY:

54701

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.704

AC:

29197

AN:

41486

American (AMR)

AF:

0.733

AC:

11200

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.796

AC:

2760

AN:

3468

East Asian (EAS)

AF:

0.678

AC:

3500

AN:

5166

South Asian (SAS)

AF:

0.771

AC:

3717

AN:

4820

European-Finnish (FIN)

AF:

0.772

AC:

8169

AN:

10586

Middle Eastern (MID)

AF:

0.733

AC:

214

AN:

292

European-Non Finnish (NFE)

AF:

0.747

AC:

50811

AN:

67992

Other (OTH)

AF:

0.740

AC:

1561

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1540

3080

4621

6161

7701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

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

Oct 25, 2021

Genome-Nilou Lab

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. -

Jun 27, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.33

(source)

DANN

Benign

0.64

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over