3-71772559-TA-T

Position:

• chr3-71772559-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001126128.2(PROK2):​c.*164delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 564,984 control chromosomes in the GnomAD database, including 590 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (585 hom., cov: 29)
  • Exomes 𝑓: 0.32 (5 hom.)
• Consequence: PROK2 NM_001126128.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.92

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 -10 ACMG points.

• BP6: Variant 3-71772559-TA-T is Benign according to our data. Variant chr3-71772559-TA-T is described in ClinVar as [Benign]. Clinvar id is 1220791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROK2	NM_001126128.2	c.*164delT		3_prime_UTR_variant	4/4	ENST00000295619.4	NP_001119600.1
PROK2	NM_021935.4	c.*164delT		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.*164delT		3_prime_UTR_variant	4/4	1	NM_001126128.2	ENSP00000295619.3
PROK2	ENST00000353065	c.*164delT		3_prime_UTR_variant	3/3	1		ENSP00000295618.3

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 8306 AN: 137160 Hom.: 579 Cov.: 29

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0309

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.00221

Gnomad EAS AF: 0.00349

Gnomad SAS AF: 0.00385

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.00753

Gnomad OTH AF: 0.0479

GnomAD4 exome AF: 0.315 AC: 134806 AN: 427760 Hom.: 5 Cov.: 0 AF XY: 0.312 AC XY: 70674 AN XY: 226792

Gnomad4 AFR exome AF: 0.347

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.0608 AC: 8340 AN: 137224 Hom.: 585 Cov.: 29 AF XY: 0.0600 AC XY: 3989 AN XY: 66476

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.00221

Gnomad4 EAS AF: 0.00370

Gnomad4 SAS AF: 0.00364

Gnomad4 FIN AF: 0.0278

Gnomad4 NFE AF: 0.00753

Gnomad4 OTH AF: 0.0480

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs56679628; hg19: chr3-71821710;