Genetic Variant NM_144773.4:c.*127T>C (chr20-5301913-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.362

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
PROKR2	NM_144773.4 link	c.*127T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000678254.1	NP_658986.1	Q8NFJ6A8K1T0
PROKR2	XM_017027646.2 link	c.*127T>C		3_prime_UTR_variant	Exon 3 of 4		XP_016883135.1	Q8NFJ6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PROKR2	ENST00000678254 link	c.*127T>C	3_prime_UTR_variant	Exon 3 of 3		NM_144773.4	ENSP00000504128.1	Q8NFJ6
PROKR2	ENST00000217270 link	c.*127T>C	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000217270.3	Q8NFJ6
PROKR2	ENST00000678059 link	c.*127T>C	3_prime_UTR_variant	Exon 3 of 3			ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes

AF:

0.729

AC:

110847

AN:

152026

Hom.:

40412

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.731

AC XY:

54361

AN XY:

74384

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over