20-5301973-A-T

Position:

• chr20-5301973-A-T

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.*67T>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 0.456 in 1,417,880 control chromosomes in the GnomAD database, including 149,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (13900 hom., cov: 32)
  • Exomes 𝑓: 0.46 (135333 hom.)
• Consequence: PROKR2 NM_144773.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00300

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=-0.72).
• BP6: Variant 20-5301973-A-T is Benign according to our data. Variant chr20-5301973-A-T is described in ClinVar as [Benign]. Clinvar id is 1291545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROKR2	NM_144773.4	c.*67T>A		3_prime_UTR_variant	3/3	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2	c.*67T>A		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.*67T>A		3_prime_UTR_variant	3/3		NM_144773.4	ENSP00000504128	P1
PROKR2	ENST00000217270.4	c.*67T>A		3_prime_UTR_variant	3/3	1		ENSP00000217270	P1
PROKR2	ENST00000678059.1	c.*67T>A		3_prime_UTR_variant	3/3			ENSP00000503366

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64596 AN: 151888 Hom.: 13877 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.459 AC: 581500 AN: 1265874 Hom.: 135333 AF XY: 0.461 AC XY: 291936 AN XY: 633054

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.458

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.425 AC: 64669 AN: 152006 Hom.: 13900 Cov.: 32 AF XY: 0.426 AC XY: 31670 AN XY: 74298

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.426

Alfa AF: 0.440 Hom.: 1852

Bravo AF: 0.415

Asia WGS AF: 0.426 AC: 1479 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	-0.72
CADD	Benign	4.1
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3746681; hg19: chr20-5282619; COSMIC: COSV54085684;