rs73071931

Variant names:

• chr20-5301912-C-T
• rs73071931
• NM_144773.4:c.*128G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144773.4(PROKR2):​c.*128G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 782,230 control chromosomes in the GnomAD database, including 5,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1181 hom., cov: 33)
  • Exomes 𝑓: 0.12 (4757 hom.)
• Consequence: PROKR2 NM_144773.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.00
• Publications: 1 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: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-5301912-C-T is Benign according to our data. Variant chr20-5301912-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 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.*128G>A		3_prime_UTR	Exon 3 of 3	NP_658986.1	Q8NFJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.*128G>A		3_prime_UTR	Exon 3 of 3	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.*128G>A		3_prime_UTR	Exon 3 of 3	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.*128G>A		3_prime_UTR	Exon 3 of 3	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18280 AN: 152102 Hom.: 1181 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0361

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.118 AC: 74528 AN: 630008 Hom.: 4757 AF XY: 0.120 AC XY: 38870 AN XY: 325064

African (AFR) AF: 0.130 AC: 2140 AN: 16506

American (AMR) AF: 0.0661 AC: 1781 AN: 26950

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 2643 AN: 16108

East Asian (EAS) AF: 0.0407 AC: 1303 AN: 32034

South Asian (SAS) AF: 0.126 AC: 6666 AN: 52770

European-Finnish (FIN) AF: 0.168 AC: 5467 AN: 32584

Middle Eastern (MID) AF: 0.0979 AC: 342 AN: 3494

European-Non Finnish (NFE) AF: 0.120 AC: 50269 AN: 417350

Other (OTH) AF: 0.122 AC: 3917 AN: 32212

GnomAD4 genome AF: 0.120 AC: 18297 AN: 152222 Hom.: 1181 Cov.: 33 AF XY: 0.122 AC XY: 9107 AN XY: 74422

African (AFR) AF: 0.130 AC: 5418 AN: 41524

American (AMR) AF: 0.0806 AC: 1234 AN: 15302

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

East Asian (EAS) AF: 0.0362 AC: 187 AN: 5172

South Asian (SAS) AF: 0.118 AC: 568 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1888 AN: 10602

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

European-Non Finnish (NFE) AF: 0.119 AC: 8120 AN: 68014

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.120 Hom.: 224

Bravo AF: 0.113

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.60
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs73071931; hg19: chr20-5282558;