16-2089712-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001009944.3(PKD1):c.*15G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,566,408 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 18 hom., cov: 34)

Exomes 𝑓: 0.012 ( 174 hom. )

Consequence

PKD1
NM_001009944.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.541

Publications

2 publications found

Variant links:

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

PKD1 links:

TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]

TSC2 Gene-Disease associations (from GenCC):

tuberous sclerosis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
tuberous sclerosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
lymphangioleiomyomatosis
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
tuberous sclerosis complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TSC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-2089712-C-T is Benign according to our data. Variant chr16-2089712-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 256884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0123 (1875/152364) while in subpopulation AMR AF = 0.0188 (288/15304). AF 95% confidence interval is 0.017. There are 18 homozygotes in GnomAd4. There are 1049 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.*15G>A		3_prime_UTR_variant	Exon 46 of 46	ENST00000262304.9	NP_001009944.3
TSC2	NM_000548.5 link	c.*1102C>T		downstream_gene_variant		ENST00000219476.9	NP_000539.2	P49815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.*15G>A		3_prime_UTR_variant	Exon 46 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1
TSC2	ENST00000219476.9 link	c.*1102C>T		downstream_gene_variant		5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1875

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0407

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.0144

AC:

2495

AN:

173144

AF XY:

0.0135

show subpopulations

Gnomad AFR exome

AF:

0.00211

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0470

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0412

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0124

AC:

17521

AN:

1414044

Hom.:

174

Cov.:

AF XY:

0.0121

AC XY:

8442

AN XY:

698910

show subpopulations

African (AFR)

AF:

0.00192

AC:

AN:

32742

American (AMR)

AF:

0.0104

AC:

382

AN:

36894

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

1159

AN:

25296

East Asian (EAS)

AF:

0.0000265

AC:

AN:

37804

South Asian (SAS)

AF:

0.00335

AC:

270

AN:

80656

European-Finnish (FIN)

AF:

0.0380

AC:

1860

AN:

48936

Middle Eastern (MID)

AF:

0.0232

AC:

AN:

4262

European-Non Finnish (NFE)

AF:

0.0119

AC:

12934

AN:

1088884

Other (OTH)

AF:

0.0129

AC:

753

AN:

58570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

921

1842

2763

3684

4605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0123

AC:

1875

AN:

152364

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1049

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

41592

American (AMR)

AF:

0.0188

AC:

288

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

136

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00331

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0407

AC:

432

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

859

AN:

68034

Other (OTH)

AF:

0.0189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

188

283

377

471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 01, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant polycystic kidney disease

Benign:2

Jul 28, 2016

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2019

Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Polycystic kidney disease, adult type

Benign:1

Feb 13, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

(source)

DANN

Benign

0.58

PhyloP100

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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16-2089712-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over