16-2102387-C-G

Position:

chr16-2102387-C-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.9195G>C(p.Val3065=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,555,570 control chromosomes in the GnomAD database, including 27,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6325 hom., cov: 33)

Exomes 𝑓: 0.16 ( 21588 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.786

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=-0.83).

BP6

Variant 16-2102387-C-G is Benign according to our data. Variant chr16-2102387-C-G is described in ClinVar as [Benign]. Clinvar id is 257039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.786 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 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.9195G>C	p.Val3065=	synonymous_variant	25/46	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.9195G>C	p.Val3065=	synonymous_variant	25/46	1	NM_001009944.3	ENSP00000262304	P5	P98161-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37356

AN:

151642

Hom.:

6306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0703

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.232

GnomAD3 exomes

AF:

0.156

AC:

24792

AN:

158570

Hom.:

2758

AF XY:

0.149

AC XY:

12566

AN XY:

84292

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.000260

Gnomad SAS exome

AF:

0.0731

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.164

AC:

229811

AN:

1403812

Hom.:

21588

Cov.:

AF XY:

0.160

AC XY:

111141

AN XY:

693440

show subpopulations

Gnomad4 AFR exome

AF:

0.495

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.000436

Gnomad4 SAS exome

AF:

0.0747

Gnomad4 FIN exome

AF:

0.181

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.247

AC:

37419

AN:

151758

Hom.:

6325

Cov.:

AF XY:

0.241

AC XY:

17871

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.482

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0698

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.156

Hom.:

719

Bravo

AF:

0.259

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	This variant is associated with the following publications: (PMID: 15772804, 10854095, 18837007, 22608885, 24374109) -
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

May 08, 2020

- -

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

-0.83

CADD

Benign

0.55

DANN

Benign

0.60

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