chr20-5302085-G-T

Variant names:

• chr20-5302085-G-T
• rs76049287
• NM_144773.4:c.1110C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144773.4(PROKR2):​c.1110C>A​(p.Asn370Lys) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N370N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PROKR2 NM_144773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• 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: 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088475466).

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.1110C>A	p.Asn370Lys	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.1110C>A	p.Asn370Lys	missense	Exon 3 of 3	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.1110C>A	p.Asn370Lys	missense	Exon 3 of 3	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.1002C>A	p.Asn334Lys	missense	Exon 3 of 3	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.15
DANN	Benign	0.94
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.25
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.19
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.048	D
Polyphen		0.0	B
Vest4		0.15
MutPred		0.41		Gain of ubiquitination at N370 (P = 0.0054)
MVP		0.43
ClinPred		0.41	T
GERP RS		-0.33
Varity_R		0.065
gMVP		0.24
Mutation Taster		=91/9	polymorphism

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: rs76049287; hg19: chr20-5282731;