rs6516015

Variant names:

• chr20-5311440-T-C
• rs6516015
• NM_144773.4:c.458+2472A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-5311440-T-C
• chr20-5311440-T-G

Variant summary

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

The NM_144773.4(PROKR2):​c.458+2472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,884 control chromosomes in the GnomAD database, including 20,092 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 0.51 (20092 hom., cov: 32)
• Consequence: PROKR2 NM_144773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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 (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROKR2	NM_144773.4	c.458+2472A>G		intron_variant	Intron 2 of 2	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2	c.458+2472A>G		intron_variant	Intron 2 of 3		XP_016883135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROKR2	ENST00000678254.1	c.458+2472A>G		intron_variant	Intron 2 of 2		NM_144773.4	ENSP00000504128.1
PROKR2	ENST00000217270.4	c.458+2472A>G		intron_variant	Intron 2 of 2	1		ENSP00000217270.3
PROKR2	ENST00000678059.1	c.350+2472A>G		intron_variant	Intron 2 of 2			ENSP00000503366.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77445 AN: 151766 Hom.: 20056 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.510 AC: 77535 AN: 151884 Hom.: 20092 Cov.: 32 AF XY: 0.511 AC XY: 37921 AN XY: 74230

African (AFR) AF: 0.614 AC: 25404 AN: 41404

American (AMR) AF: 0.421 AC: 6429 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1675 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2808 AN: 5170

South Asian (SAS) AF: 0.512 AC: 2459 AN: 4804

European-Finnish (FIN) AF: 0.489 AC: 5157 AN: 10540

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32124 AN: 67924

Other (OTH) AF: 0.487 AC: 1026 AN: 2106

Alfa AF: 0.458 Hom.: 7899

Bravo AF: 0.506

Asia WGS AF: 0.468 AC: 1626 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	0.54
DANN	Benign	0.68
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6516015; hg19: chr20-5292086;