chr20-5311114-T-C

Variant names:

• chr20-5311114-T-C
• rs6053291
• NM_144773.4:c.458+2798A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144773.4(PROKR2):​c.458+2798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,038 control chromosomes in the GnomAD database, including 20,110 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 0.51 (20110 hom., cov: 32)
• Consequence: PROKR2 NM_144773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Laboratory for Molecular Medicine
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 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.458+2798A>G		intron	N/A	NP_658986.1	Q8NFJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.458+2798A>G		intron	N/A	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.458+2798A>G		intron	N/A	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.350+2798A>G		intron	N/A	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77499 AN: 151920 Hom.: 20074 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.510 AC: 77589 AN: 152038 Hom.: 20110 Cov.: 32 AF XY: 0.511 AC XY: 37943 AN XY: 74310

African (AFR) AF: 0.614 AC: 25456 AN: 41486

American (AMR) AF: 0.421 AC: 6441 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2802 AN: 5160

South Asian (SAS) AF: 0.511 AC: 2465 AN: 4824

European-Finnish (FIN) AF: 0.489 AC: 5157 AN: 10544

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 32115 AN: 67946

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.491 Hom.: 2433

Bravo AF: 0.506

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.72
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6053291; hg19: chr20-5291760;