rs3746682

Variant names:

• chr20-5302610-C-G
• rs3746682
• NM_144773.4:c.585G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-5302610-C-G
• chr20-5302610-C-A
• chr20-5302610-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.51
• Publications: 29 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Laboratory for Molecular Medicine
• 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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	NM_144773.4	MANE Select	c.585G>C	p.Thr195Thr	synonymous	Exon 3 of 3	NP_658986.1	Q8NFJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.585G>C	p.Thr195Thr	synonymous	Exon 3 of 3	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.585G>C	p.Thr195Thr	synonymous	Exon 3 of 3	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.477G>C	p.Thr159Thr	synonymous	Exon 3 of 3	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111570 AN: 152002 Hom.: 40921 Cov.: 32

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

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.: 64 AF XY: 0.751 AC XY: 546485 AN XY: 727220

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

GnomAD4 genome AF: 0.734 AC: 111677 AN: 152120 Hom.: 40975 Cov.: 32 AF XY: 0.736 AC XY: 54701 AN XY: 74362

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hypogonadotropic hypogonadism 3 with or without anosmia (3)
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.64
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3746682; hg19: chr20-5283256; COSMIC: COSV54088265;