NM_144773.4:c.*879C>T

Variant names:

• chr20-5301161-G-A
• rs4815787
• NM_144773.4:c.*879C>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.*879C>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 0.451 in 151,904 control chromosomes in the GnomAD database, including 15,712 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 0.45 (15712 hom., cov: 32)
• Consequence: PROKR2 NM_144773.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	NM_144773.4	MANE Select	c.*879C>T		3_prime_UTR	Exon 3 of 3	NP_658986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.*879C>T		3_prime_UTR	Exon 3 of 3	ENSP00000504128.1
	PROKR2	ENST00000217270.4	TSL:1	c.*879C>T		3_prime_UTR	Exon 3 of 3	ENSP00000217270.3
	PROKR2	ENST00000678059.1		c.*879C>T		3_prime_UTR	Exon 3 of 3	ENSP00000503366.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68386 AN: 151786 Hom.: 15698 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.451 AC: 68442 AN: 151904 Hom.: 15712 Cov.: 32 AF XY: 0.452 AC XY: 33554 AN XY: 74244

African (AFR) AF: 0.359 AC: 14880 AN: 41410

American (AMR) AF: 0.397 AC: 6061 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2274 AN: 5162

South Asian (SAS) AF: 0.536 AC: 2587 AN: 4824

European-Finnish (FIN) AF: 0.492 AC: 5172 AN: 10512

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34223 AN: 67930

Other (OTH) AF: 0.450 AC: 953 AN: 2116

Alfa AF: 0.470 Hom.: 2118

Bravo AF: 0.438

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.66
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs4815787; hg19: chr20-5281807;