dbSNP rs6085086: PROKR2:c.458+1432C>T (chr20-5312480-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144773.4(PROKR2):c.458+1432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,110 control chromosomes in the GnomAD database, including 7,385 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7385 hom., cov: 33)

Consequence

PROKR2
NM_144773.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.176

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROKR2	NM_144773.4 link	c.458+1432C>T		intron_variant	Intron 2 of 2	ENST00000678254.1	NP_658986.1	Q8NFJ6A8K1T0
PROKR2	XM_017027646.2 link	c.458+1432C>T		intron_variant	Intron 2 of 3		XP_016883135.1	Q8NFJ6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PROKR2	ENST00000678254.1 link	c.458+1432C>T	intron_variant	Intron 2 of 2		NM_144773.4	ENSP00000504128.1	Q8NFJ6
PROKR2	ENST00000217270.4 link	c.458+1432C>T	intron_variant	Intron 2 of 2	1		ENSP00000217270.3	Q8NFJ6
PROKR2	ENST00000678059.1 link	c.350+1432C>T	intron_variant	Intron 2 of 2			ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46631

AN:

151992

Hom.:

7376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.307

AC:

46659

AN:

152110

Hom.:

7385

Cov.:

AF XY:

0.305

AC XY:

22646

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.241

AC:

9987

AN:

41498

American (AMR)

AF:

0.250

AC:

3816

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1116

AN:

3468

East Asian (EAS)

AF:

0.390

AC:

2014

AN:

5170

South Asian (SAS)

AF:

0.354

AC:

1708

AN:

4830

European-Finnish (FIN)

AF:

0.295

AC:

3120

AN:

10572

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.351

AC:

23871

AN:

67976

Other (OTH)

AF:

0.308

AC:

649

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1658

3315

4973

6630

8288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.231

Hom.:

683

Bravo

AF:

0.298

Asia WGS

AF:

0.298

AC:

1036

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.4

(source)

DANN

Benign

0.75

PhyloP100

0.18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over