3-71772559-T-TA

Position:

• chr3-71772559-T-TA

Variant summary

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

The NM_001126128.2(PROK2):​c.*164dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 596,012 control chromosomes in the GnomAD database, including 1,002 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (991 hom., cov: 29)
  • Exomes 𝑓: 0.10 (11 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-T-TA is Benign according to our data. Variant chr3-71772559-T-TA is described in ClinVar as [Benign]. Clinvar id is 1239728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.108 AC: 14894 AN: 137528 Hom.: 989 Cov.: 29

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0728

Gnomad OTH AF: 0.0974

GnomAD4 exome AF: 0.103 AC: 47402 AN: 458416 Hom.: 11 Cov.: 0 AF XY: 0.109 AC XY: 26413 AN XY: 242680

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.0881

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.0708

Gnomad4 NFE exome AF: 0.0837

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.108 AC: 14902 AN: 137596 Hom.: 991 Cov.: 29 AF XY: 0.116 AC XY: 7709 AN XY: 66712

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0728

Gnomad4 OTH AF: 0.0951

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 18, 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;