3-71772559-TAA-T

Position:

• chr3-71772559-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001126128.2(PROK2):​c.*163_*164delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 581,324 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (11 hom., cov: 29)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: PROK2 NM_001126128.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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-TAA-T is Benign according to our data. Variant chr3-71772559-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1219630.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00687 (945/137590) while in subpopulation AFR AF= 0.0221 (851/38462). AF 95% confidence interval is 0.0209. There are 11 homozygotes in gnomad4. There are 434 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROK2	NM_001126128.2	c.*163_*164delTT		3_prime_UTR_variant	4/4	ENST00000295619.4	NP_001119600.1
PROK2	NM_021935.4	c.*163_*164delTT		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.*163_*164delTT		3_prime_UTR_variant	4/4	1	NM_001126128.2	ENSP00000295619.3
PROK2	ENST00000353065	c.*163_*164delTT		3_prime_UTR_variant	3/3	1		ENSP00000295618.3

Frequencies

GnomAD3 genomes AF: 0.00686 AC: 944 AN: 137526 Hom.: 11 Cov.: 29

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00204

Gnomad ASJ AF: 0.00220

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000905

Gnomad FIN AF: 0.000617

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000696

Gnomad OTH AF: 0.00372

GnomAD4 exome AF: 0.0192 AC: 8521 AN: 443734 Hom.: 0 AF XY: 0.0187 AC XY: 4408 AN XY: 235180

Gnomad4 AFR exome AF: 0.0530

Gnomad4 AMR exome AF: 0.0218

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.0132

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0177

Gnomad4 NFE exome AF: 0.0194

Gnomad4 OTH exome AF: 0.0202

GnomAD4 genome AF: 0.00687 AC: 945 AN: 137590 Hom.: 11 Cov.: 29 AF XY: 0.00651 AC XY: 434 AN XY: 66698

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00220

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000908

Gnomad4 FIN AF: 0.000617

Gnomad4 NFE AF: 0.000696

Gnomad4 OTH AF: 0.00370

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 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;