20-5301973-A-G

Variant names:

• chr20-5301973-A-G
• rs3746681
• NM_144773.4:c.*67T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144773.4(PROKR2):​c.*67T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PROKR2 NM_144773.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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.*67T>C		3_prime_UTR	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.*67T>C		3_prime_UTR	Exon 3 of 3	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.*67T>C		3_prime_UTR	Exon 3 of 3	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.*67T>C		3_prime_UTR	Exon 3 of 3	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1268500 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 634388

African (AFR) AF: 0.00 AC: 0 AN: 29754

American (AMR) AF: 0.00 AC: 0 AN: 41762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23826

East Asian (EAS) AF: 0.00 AC: 0 AN: 37962

South Asian (SAS) AF: 0.00 AC: 0 AN: 78232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 950802

Other (OTH) AF: 0.00 AC: 0 AN: 53810

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.5
DANN	Benign	0.88
PhyloP100		0.0030

Splicing

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

Other links and lift over

dbSNP: rs3746681; hg19: chr20-5282619;