rs10485485

Variant names:

• chr20-5303734-T-C
• rs10485485
• NM_144773.4:c.459-998A>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.459-998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,992 control chromosomes in the GnomAD database, including 958 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 0.11 (958 hom., cov: 31)
• Consequence: PROKR2 NM_144773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROKR2	NM_144773.4	c.459-998A>G		intron_variant	Intron 2 of 2	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2	c.459-998A>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.459-998A>G		intron_variant	Intron 2 of 2		NM_144773.4	ENSP00000504128.1
PROKR2	ENST00000217270.4	c.459-998A>G		intron_variant	Intron 2 of 2	1		ENSP00000217270.3
PROKR2	ENST00000678059.1	c.351-998A>G		intron_variant	Intron 2 of 2			ENSP00000503366.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16227 AN: 151874 Hom.: 959 Cov.: 31

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0769

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.107 AC: 16228 AN: 151992 Hom.: 958 Cov.: 31 AF XY: 0.109 AC XY: 8118 AN XY: 74294

African (AFR) AF: 0.0837 AC: 3470 AN: 41452

American (AMR) AF: 0.0767 AC: 1170 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3470

East Asian (EAS) AF: 0.0367 AC: 189 AN: 5154

South Asian (SAS) AF: 0.116 AC: 560 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1878 AN: 10544

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8105 AN: 67988

Other (OTH) AF: 0.108 AC: 228 AN: 2110

Alfa AF: 0.115 Hom.: 1665

Bravo AF: 0.0981

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.71
PhyloP100		0.19
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: rs10485485; hg19: chr20-5284380;