chr16-2089126-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001009944.3(PKD1):c.*601T>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 0.276 in 169,558 control chromosomes in the GnomAD database, including 9,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 9233 hom., cov: 34)

Exomes 𝑓: 0.15 ( 262 hom. )

Consequence

PKD1
NM_001009944.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0540

Publications

19 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-2089126-A-T is Benign according to our data. Variant chr16-2089126-A-T is described in ClinVar as Benign. ClinVar VariationId is 3780389.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.*601T>A		3_prime_UTR_variant	Exon 46 of 46	ENST00000262304.9	NP_001009944.3
TSC2	NM_000548.5 link	c.*516A>T		3_prime_UTR_variant	Exon 42 of 42	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.*601T>A		3_prime_UTR_variant	Exon 46 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1
TSC2	ENST00000219476.9 link	c.*516A>T		3_prime_UTR_variant	Exon 42 of 42	5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44125

AN:

152020

Hom.:

9199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.587

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0937

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.258

GnomAD4 exome

AF:

0.153

AC:

2665

AN:

17420

Hom.:

262

Cov.:

AF XY:

0.154

AC XY:

1374

AN XY:

8926

show subpopulations

African (AFR)

AF:

0.513

AC:

154

AN:

300

American (AMR)

AF:

0.150

AC:

375

AN:

2506

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

AN:

346

East Asian (EAS)

AF:

0.00

AC:

AN:

1060

South Asian (SAS)

AF:

0.0917

AC:

148

AN:

1614

European-Finnish (FIN)

AF:

0.180

AC:

AN:

356

Middle Eastern (MID)

AF:

0.262

AC:

AN:

European-Non Finnish (NFE)

AF:

0.162

AC:

1688

AN:

10402

Other (OTH)

AF:

0.195

AC:

155

AN:

794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

105

210

315

420

525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.291

AC:

44213

AN:

152138

Hom.:

9233

Cov.:

AF XY:

0.287

AC XY:

21332

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.587

AC:

24361

AN:

41482

American (AMR)

AF:

0.207

AC:

3167

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

873

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5176

South Asian (SAS)

AF:

0.0934

AC:

451

AN:

4830

European-Finnish (FIN)

AF:

0.232

AC:

2454

AN:

10596

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.179

AC:

12158

AN:

67968

Other (OTH)

AF:

0.255

AC:

539

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1328

2655

3983

5310

6638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.239

Hom.:

844

Bravo

AF:

0.303

Asia WGS

AF:

0.0840

AC:

293

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal dominant polycystic kidney disease

Benign:1

Feb 19, 2016

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.3

(source)

DANN

Benign

0.56

PhyloP100

0.054

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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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