3-71772782-G-T

Position:

chr3-71772782-G-T

Variant summary

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

The NM_001126128.2(PROK2):c.332C>A(p.Pro111Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000947 in 1,614,160 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 5 hom. )

Consequence

PROK2
NM_001126128.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 8.65

Variant links:

Genes affected

PROK2 (HGNC:18455): (prokineticin 2) This gene encodes a protein expressed in the suprachiasmatic nucleus (SCN) circadian clock that may function as the output component of the circadian clock. The secreted form of the encoded protein may also serve as a chemoattractant for neuronal precursor cells in the olfactory bulb. Proteins from other vertebrates which are similar to this gene product were isolated based on homology to snake venom and secretions from frog skin, and have been shown to have diverse functions. Mutations in this gene are associated with Kallmann syndrome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PROK2 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=0.009821266).

BP6

Variant 3-71772782-G-T is Benign according to our data. Variant chr3-71772782-G-T is described in ClinVar as [Benign]. Clinvar id is 695610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00523 (796/152282) while in subpopulation AFR AF= 0.0185 (767/41554). AF 95% confidence interval is 0.0174. There are 10 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROK2	NM_001126128.2 linkuse as main transcript	c.332C>A	p.Pro111Gln	missense_variant	4/4	ENST00000295619.4	NP_001119600.1	Q9HC23-1
PROK2	NM_021935.4 linkuse as main transcript	c.269C>A	p.Pro90Gln	missense_variant	3/3		NP_068754.1	Q9HC23-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROK2	ENST00000295619.4 linkuse as main transcript	c.332C>A	p.Pro111Gln	missense_variant	4/4	1	NM_001126128.2	ENSP00000295619.3		Q9HC23-1
PROK2	ENST00000353065.7 linkuse as main transcript	c.269C>A	p.Pro90Gln	missense_variant	3/3	1		ENSP00000295618.3		Q9HC23-2

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

795

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00135

AC:

340

AN:

251370

Hom.:

AF XY:

0.00102

AC XY:

139

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0190

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000501

AC:

733

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

340

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00523

AC:

796

AN:

152282

Hom.:

Cov.:

AF XY:

0.00496

AC XY:

369

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000926

Hom.:

Bravo

AF:

0.00598

ESP6500AA

AF:

0.0195

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00170

AC:

207

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2020	This variant is associated with the following publications: (PMID: 31200363) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 27, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.86

.;D

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

MetaRNN

Benign

0.0098

T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.52

Sift

Benign

0.072

T;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

.;D

Vest4

0.61

MVP

0.97

MPC

0.48

ClinPred

0.028

GERP RS

5.8

Varity_R

0.66

gMVP

0.65

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