rs2099534

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001009944.3(PKD1):c.3111A>G(p.Leu1037Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 1,599,938 control chromosomes in the GnomAD database, including 2,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 166 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2425 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.64

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:

ENSG00000261240 (HGNC:):

ENSG00000261240 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 16-2112838-T-C is Benign according to our data. Variant chr16-2112838-T-C is described in ClinVar as [Benign]. Clinvar id is 256944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2112838-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.3111A>G	p.Leu1037Leu	synonymous_variant	Exon 13 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.3111A>G	p.Leu1037Leu	synonymous_variant	Exon 13 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0379

AC:

5763

AN:

152194

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0398

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0432

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0587

Gnomad OTH

AF:

0.0575

GnomAD3 exomes

AF:

0.0378

AC:

9226

AN:

244380

Hom.:

236

AF XY:

0.0383

AC XY:

5099

AN XY:

133062

show subpopulations

Gnomad AFR exome

AF:

0.00938

Gnomad AMR exome

AF:

0.0292

Gnomad ASJ exome

AF:

0.0331

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00591

Gnomad FIN exome

AF:

0.0471

Gnomad NFE exome

AF:

0.0579

Gnomad OTH exome

AF:

0.0451

GnomAD4 exome

AF:

0.0521

AC:

75491

AN:

1447626

Hom.:

2425

Cov.:

AF XY:

0.0508

AC XY:

36584

AN XY:

720570

show subpopulations

Gnomad4 AFR exome

AF:

0.00848

Gnomad4 AMR exome

AF:

0.0316

Gnomad4 ASJ exome

AF:

0.0348

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00578

Gnomad4 FIN exome

AF:

0.0448

Gnomad4 NFE exome

AF:

0.0607

Gnomad4 OTH exome

AF:

0.0496

GnomAD4 genome

AF:

0.0378

AC:

5761

AN:

152312

Hom.:

166

Cov.:

AF XY:

0.0364

AC XY:

2714

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0100

Gnomad4 AMR

AF:

0.0397

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.0432

Gnomad4 NFE

AF:

0.0588

Gnomad4 OTH

AF:

0.0569

Alfa

AF:

0.0438

Hom.:

Bravo

AF:

0.0381

EpiCase

AF:

0.0621

EpiControl

AF:

0.0617

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 13, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10364515, 22383692, 15772804, 11857740, 17574468, 22008521, 18837007) -

Polycystic kidney disease, adult type

Benign:2

Jun 05, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 15, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant polycystic kidney disease

Benign:1

Jan 01, 2019

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.1

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over