rs142606648

Positions:

chr16-2114368-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000262304.9(PKD1):c.2655C>T(p.Cys885=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000685 in 1,609,636 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 2 hom. )

Consequence

PKD1
ENST00000262304.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.72

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:

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=-0.9).

BP6

Variant 16-2114368-G-A is Benign according to our data. Variant chr16-2114368-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2114368-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.72 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000683 (996/1457362) while in subpopulation EAS AF= 0.00716 (284/39692). AF 95% confidence interval is 0.00647. There are 2 homozygotes in gnomad4_exome. There are 508 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1	NM_001009944.3 linkuse as main transcript	c.2655C>T	p.Cys885=	synonymous_variant	11/46	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.2655C>T	p.Cys885=	synonymous_variant	11/46	1	NM_001009944.3	ENSP00000262304	P5	P98161-1

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00675

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000949

AC:

233

AN:

245394

Hom.:

AF XY:

0.000933

AC XY:

125

AN XY:

134038

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00634

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00101

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

AF:

0.000683

AC:

996

AN:

1457362

Hom.:

Cov.:

AF XY:

0.000701

AC XY:

508

AN XY:

725032

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00716

Gnomad4 SAS exome

AF:

0.000801

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.000451

Gnomad4 OTH exome

AF:

0.000848

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152274

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00657

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000853

Hom.:

Bravo

AF:

0.000601

EpiCase

AF:

0.000709

EpiControl

AF:

0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 02, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 18, 2020	- -

PKD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.23

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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