20-5314027-C-A

Variant names:

• chr20-5314027-C-A
• NM_144773.4:c.343G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_144773.4(PROKR2):​c.343G>T​(p.Val115Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V115M) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PROKR2 NM_144773.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr20-5314027-C-T is described in Lovd as [Pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROKR2	NM_144773.4	c.343G>T	p.Val115Leu	missense_variant	Exon 2 of 3	ENST00000678254.1	NP_658986.1
PROKR2	XM_017027646.2	c.343G>T	p.Val115Leu	missense_variant	Exon 2 of 4		XP_016883135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROKR2	ENST00000678254.1	c.343G>T	p.Val115Leu	missense_variant	Exon 2 of 3		NM_144773.4	ENSP00000504128.1
PROKR2	ENST00000217270.4	c.343G>T	p.Val115Leu	missense_variant	Exon 2 of 3	1		ENSP00000217270.3
PROKR2	ENST00000678059.1	c.235G>T	p.Val79Leu	missense_variant	Exon 2 of 3			ENSP00000503366.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.52
Sift	Benign	0.13	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.89
MutPred		0.77		Gain of helix (P = 0.2684);
MVP		0.85
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.49
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-5294673;