rs2457533

Positions:

chr16-2106849-A-G

Variant summary

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

The NM_001009944.3(PKD1):c.7165T>C(p.Leu2389Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,378,590 control chromosomes in the GnomAD database, including 18,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 7297 hom., cov: 30)

Exomes 𝑓: 0.094 ( 11660 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.26

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:

PKD1 (HGNC:):

PKD1 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=-0.61).

BP6

Variant 16-2106849-A-G is Benign according to our data. Variant chr16-2106849-A-G is described in ClinVar as [Benign]. Clinvar id is 256997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2106849-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=3.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1	NM_001009944.3 linkuse as main transcript	c.7165T>C	p.Leu2389Leu	synonymous_variant	17/46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 linkuse as main transcript	c.7165T>C	p.Leu2389Leu	synonymous_variant	17/46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40243

AN:

150008

Hom.:

7270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.0317

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.143

AC:

27649

AN:

192938

Hom.:

3152

AF XY:

0.140

AC XY:

14961

AN XY:

107240

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.0207

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.0943

AC:

115809

AN:

1228468

Hom.:

11660

Cov.:

AF XY:

0.0944

AC XY:

58085

AN XY:

615468

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.0908

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.0347

Gnomad4 SAS exome

AF:

0.0891

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.0807

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.269

AC:

40313

AN:

150122

Hom.:

7297

Cov.:

AF XY:

0.265

AC XY:

19432

AN XY:

73274

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.0314

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.239

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.227

Hom.:

925

Bravo

AF:

0.281

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 29, 2019	This variant is associated with the following publications: (PMID: 22608885) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Polycystic kidney disease, adult type

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 07, 2020

- -

Polycystic kidney disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The c.7165T>C , p.Leu2389Leu variant was identified in 18.75% of 8483 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

Benign, criteria provided, single submitter

research

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

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.7

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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