Genetic Variant PROK2:c.*162_*164dupTTT (chr3-71772559-T-TAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001126128.2(PROK2):c.*162_*164dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 602,148 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PROK2
NM_001126128.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

Publications

0 publications found

Variant links:

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]

PROK2 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 4 with or without anosmia
Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PROK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126128.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROK2	NM_001126128.2	MANE Select	c.162_164dupTTT		3_prime_UTR	Exon 4 of 4	NP_001119600.1	Q9HC23-1
	PROK2	NM_021935.4		c.162_164dupTTT		3_prime_UTR	Exon 3 of 3	NP_068754.1	Q9HC23-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROK2	ENST00000295619.4	TSL:1 MANE Select	c.162_164dupTTT		3_prime_UTR	Exon 4 of 4	ENSP00000295619.3	Q9HC23-1
	PROK2	ENST00000353065.7	TSL:1	c.162_164dupTTT		3_prime_UTR	Exon 3 of 3	ENSP00000295618.3	Q9HC23-2

Frequencies

GnomAD3 genomes

AF:

0.0000436

AC:

AN:

137646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00123

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

AN:

464434

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

245964

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

12284

American (AMR)

AF:

0.000239

AC:

AN:

16726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13444

East Asian (EAS)

AF:

0.00114

AC:

AN:

28876

South Asian (SAS)

AF:

0.0000946

AC:

AN:

42270

European-Finnish (FIN)

AF:

0.0000271

AC:

AN:

36934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2220

European-Non Finnish (NFE)

AF:

0.0000524

AC:

AN:

286174

Other (OTH)

AF:

0.000157

AC:

AN:

25506

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.277

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000436

AC:

AN:

137714

Hom.:

Cov.:

AF XY:

0.0000599

AC XY:

AN XY:

66764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38476

American (AMR)

AF:

0.00

AC:

AN:

13774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3182

East Asian (EAS)

AF:

0.00123

AC:

AN:

4868

South Asian (SAS)

AF:

0.00

AC:

AN:

4404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61836

Other (OTH)

AF:

0.00

AC:

AN:

1896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.9

Splicing

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

Publications

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3-71772559-TAAAAA-TAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over