rs6085086

Variant names:

• chr20-5312480-G-A
• rs6085086
• NM_144773.4:c.458+1432C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-5312480-G-A
• chr20-5312480-G-C

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+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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 2 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 -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.

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.458+1432C>T		intron	N/A	NP_658986.1	Q8NFJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.458+1432C>T		intron	N/A	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.458+1432C>T		intron	N/A	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.350+1432C>T		intron	N/A	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46631 AN: 151992 Hom.: 7376 Cov.: 33

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.: 33 AF XY: 0.305 AC XY: 22646 AN XY: 74350

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		0.18
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: rs6085086; hg19: chr20-5293126;