rs2369068

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.3063T>C(p.Gly1021Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,606,556 control chromosomes in the GnomAD database, including 15,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 5073 hom., cov: 33)

Exomes 𝑓: 0.10 ( 10630 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.34

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=-0.59).

BP6

Variant 16-2112886-A-G is Benign according to our data. Variant chr16-2112886-A-G is described in ClinVar as [Benign]. Clinvar id is 256942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2112886-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.3063T>C	p.Gly1021Gly	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.3063T>C	p.Gly1021Gly	synonymous_variant	Exon 13 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29808

AN:

151862

Hom.:

5057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0285

Gnomad FIN

AF:

0.0762

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.0993

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.105

AC:

25957

AN:

246982

Hom.:

2781

AF XY:

0.0966

AC XY:

12964

AN XY:

134200

show subpopulations

Gnomad AFR exome

AF:

0.472

Gnomad AMR exome

AF:

0.0819

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0294

Gnomad FIN exome

AF:

0.0699

Gnomad NFE exome

AF:

0.0991

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.102

AC:

147802

AN:

1454576

Hom.:

10630

Cov.:

AF XY:

0.0988

AC XY:

71494

AN XY:

723778

show subpopulations

Gnomad4 AFR exome

AF:

0.473

Gnomad4 AMR exome

AF:

0.0900

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0321

Gnomad4 FIN exome

AF:

0.0676

Gnomad4 NFE exome

AF:

0.0991

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.197

AC:

29867

AN:

151980

Hom.:

5073

Cov.:

AF XY:

0.189

AC XY:

14023

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.459

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0281

Gnomad4 FIN

AF:

0.0762

Gnomad4 NFE

AF:

0.0993

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.140

Hom.:

559

Bravo

AF:

0.215

Asia WGS

AF:

0.0440

AC:

156

AN:

3478

EpiCase

AF:

0.111

EpiControl

AF:

0.114

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 27, 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

- -

Polycystic kidney disease, adult type

Benign:2

Jun 05, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Dec 30, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10364515) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Polycystic kidney disease

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

The c.3063T>C, p.Gly1021Gly variant was identified in 11% of 13209 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015). -

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

-0.59

CADD

Benign

2.6

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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