NM_144773.4:c.-8-1055C>T

Variant names:

• chr20-5315432-G-A
• rs17721321
• NM_144773.4:c.-8-1055C>T

Variant summary

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

The NM_144773.4(PROKR2):​c.-8-1055C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,112 control chromosomes in the GnomAD database, including 3,669 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 0.21 (3669 hom., cov: 32)
• Consequence: PROKR2 NM_144773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 4 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.241 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	NM_144773.4	MANE Select	c.-8-1055C>T		intron	N/A	NP_658986.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.-8-1055C>T		intron	N/A	ENSP00000504128.1
	PROKR2	ENST00000217270.4	TSL:1	c.-9+908C>T		intron	N/A	ENSP00000217270.3
	PROKR2	ENST00000678059.1		c.-23+1062C>T		intron	N/A	ENSP00000503366.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32328 AN: 151994 Hom.: 3669 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.213 AC: 32346 AN: 152112 Hom.: 3669 Cov.: 32 AF XY: 0.212 AC XY: 15782 AN XY: 74350

African (AFR) AF: 0.142 AC: 5895 AN: 41542

American (AMR) AF: 0.247 AC: 3774 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1019 AN: 3472

East Asian (EAS) AF: 0.120 AC: 621 AN: 5162

South Asian (SAS) AF: 0.201 AC: 969 AN: 4818

European-Finnish (FIN) AF: 0.265 AC: 2802 AN: 10560

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16581 AN: 67958

Other (OTH) AF: 0.232 AC: 488 AN: 2106

Alfa AF: 0.238 Hom.: 5868

Bravo AF: 0.211

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		0.012
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: rs17721321; hg19: chr20-5296078;