20-5300607-G-A

Variant names:

• chr20-5300607-G-A
• rs4815785
• NM_144773.4:c.*1433C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144773.4(PROKR2):​c.*1433C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,094 control chromosomes in the GnomAD database, including 40,654 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 0.73 (40654 hom., cov: 33)
• Consequence: PROKR2 NM_144773.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 3 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: 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROKR2	NM_144773.4	c.*1433C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2	c.*1433C>T		3_prime_UTR_variant	Exon 3 of 4		XP_016883135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROKR2	ENST00000678254.1	c.*1433C>T		3_prime_UTR_variant	Exon 3 of 3		NM_144773.4	ENSP00000504128.1
PROKR2	ENST00000217270.4	c.*1433C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000217270.3
PROKR2	ENST00000678059.1	c.*1433C>T		3_prime_UTR_variant	Exon 3 of 3			ENSP00000503366.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111133 AN: 151976 Hom.: 40611 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.731 AC: 111226 AN: 152094 Hom.: 40654 Cov.: 33 AF XY: 0.733 AC XY: 54504 AN XY: 74342

African (AFR) AF: 0.688 AC: 28511 AN: 41460

American (AMR) AF: 0.731 AC: 11173 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2749 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3566 AN: 5190

South Asian (SAS) AF: 0.769 AC: 3704 AN: 4816

European-Finnish (FIN) AF: 0.774 AC: 8195 AN: 10584

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 51012 AN: 67976

Other (OTH) AF: 0.738 AC: 1552 AN: 2104

Alfa AF: 0.746 Hom.: 62910

Bravo AF: 0.727

Asia WGS AF: 0.694 AC: 2412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4815785; hg19: chr20-5281253;