3-71772588-A-G

Position:

• chr3-71772588-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001126128.2(PROK2):​c.*136T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00167 in 772,788 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (1 hom.)
• Consequence: PROK2 NM_001126128.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.83

Genes affected

PROK2 (HGNC:18455): (prokineticin 2) This gene encodes a protein expressed in the suprachiasmatic nucleus (SCN) circadian clock that may function as the output component of the circadian clock. The secreted form of the encoded protein may also serve as a chemoattractant for neuronal precursor cells in the olfactory bulb. Proteins from other vertebrates which are similar to this gene product were isolated based on homology to snake venom and secretions from frog skin, and have been shown to have diverse functions. Mutations in this gene are associated with Kallmann syndrome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-71772588-A-G is Benign according to our data. Variant chr3-71772588-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1211683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00588 (895/152292) while in subpopulation AFR AF= 0.0208 (863/41564). AF 95% confidence interval is 0.0196. There are 12 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROK2	NM_001126128.2	c.*136T>C		3_prime_UTR_variant	4/4	ENST00000295619.4	NP_001119600.1
PROK2	NM_021935.4	c.*136T>C		3_prime_UTR_variant	3/3		NP_068754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROK2	ENST00000295619	c.*136T>C		3_prime_UTR_variant	4/4	1	NM_001126128.2	ENSP00000295619.3
PROK2	ENST00000353065	c.*136T>C		3_prime_UTR_variant	3/3	1		ENSP00000295618.3

Frequencies

GnomAD3 genomes AF: 0.00589 AC: 897 AN: 152174 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.000635 AC: 394 AN: 620496 Hom.: 1 Cov.: 8 AF XY: 0.000482 AC XY: 159 AN XY: 329770

Gnomad4 AFR exome AF: 0.0200

Gnomad4 AMR exome AF: 0.000779

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000582

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000413

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00588 AC: 895 AN: 152292 Hom.: 12 Cov.: 32 AF XY: 0.00569 AC XY: 424 AN XY: 74478

Gnomad4 AFR AF: 0.0208

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00537 Hom.: 0

Bravo AF: 0.00693

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.3
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs150696999; hg19: chr3-71821739;