rs745562390

Variant names:

• chr20-5302139-C-A
• rs745562390
• NM_144773.4:c.1056G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-5302139-C-A
• chr20-5302139-C-G
• chr20-5302139-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144773.4(PROKR2):​c.1056G>T​(p.Trp352Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PROKR2 NM_144773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.59
• Publications: 0 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: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1056G>T	p.Trp352Cys	missense	Exon 3 of 3	NP_658986.1	Q8NFJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.1056G>T	p.Trp352Cys	missense	Exon 3 of 3	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.1056G>T	p.Trp352Cys	missense	Exon 3 of 3	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.948G>T	p.Trp316Cys	missense	Exon 3 of 3	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.22
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.50		Gain of catalytic residue at W352 (P = 0.0208)
MVP		0.58
ClinPred		0.92	D
GERP RS		3.1
Varity_R		0.27
gMVP		0.88
Mutation Taster		=41/59	disease causing

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: rs745562390; hg19: chr20-5282785;