20-5301913-A-G

Position:

• chr20-5301913-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144773.4(PROKR2):​c.*127T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 800,984 control chromosomes in the GnomAD database, including 221,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40456 hom., cov: 32)
  • Exomes 𝑓: 0.75 (181290 hom.)
• Consequence: PROKR2 NM_144773.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.362

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-5301913-A-G is Benign according to our data. Variant chr20-5301913-A-G is described in ClinVar as [Benign]. Clinvar id is 1232229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROKR2	NM_144773.4	c.*127T>C		3_prime_UTR_variant	3/3	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2	c.*127T>C		3_prime_UTR_variant	3/4		XP_016883135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROKR2	ENST00000678254.1	c.*127T>C		3_prime_UTR_variant	3/3		NM_144773.4	ENSP00000504128	P1
PROKR2	ENST00000217270.4	c.*127T>C		3_prime_UTR_variant	3/3	1		ENSP00000217270	P1
PROKR2	ENST00000678059.1	c.*127T>C		3_prime_UTR_variant	3/3			ENSP00000503366

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110847 AN: 152026 Hom.: 40412 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.739

GnomAD4 exome AF: 0.746 AC: 484230 AN: 648840 Hom.: 181290 AF XY: 0.748 AC XY: 249837 AN XY: 333788

Gnomad4 AFR exome AF: 0.682

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.793

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.752

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.729 AC: 110941 AN: 152144 Hom.: 40456 Cov.: 32 AF XY: 0.731 AC XY: 54361 AN XY: 74384

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.739

Alfa AF: 0.701 Hom.: 8458

Bravo AF: 0.725

Asia WGS AF: 0.695 AC: 2414 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3746680; hg19: chr20-5282559;