rs35965348

Positions:

chr16-2114293-G-A

Variant summary

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

The NM_001009944.3(PKD1):c.2730C>T(p.Asp910=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,610,168 control chromosomes in the GnomAD database, including 3,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 269 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3218 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.50

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=-0.72).

BP6

Variant 16-2114293-G-A is Benign according to our data. Variant chr16-2114293-G-A is described in ClinVar as [Benign]. Clinvar id is 256937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2114293-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0645 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.2730C>T	p.Asp910=	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.2730C>T	p.Asp910=	synonymous_variant	11/46	1	NM_001009944.3	ENSP00000262304	P5	P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7560

AN:

152184

Hom.:

269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0456

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.0434

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0545

AC:

13532

AN:

248208

Hom.:

469

AF XY:

0.0563

AC XY:

7591

AN XY:

134940

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.0858

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0417

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.0671

Gnomad OTH exome

AF:

0.0608

GnomAD4 exome

AF:

0.0633

AC:

92251

AN:

1457866

Hom.:

3218

Cov.:

AF XY:

0.0630

AC XY:

45692

AN XY:

725284

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.0291

Gnomad4 ASJ exome

AF:

0.0881

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0417

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.0676

Gnomad4 OTH exome

AF:

0.0584

GnomAD4 genome

AF:

0.0496

AC:

7558

AN:

152302

Hom.:

269

Cov.:

AF XY:

0.0523

AC XY:

3897

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0456

Gnomad4 ASJ

AF:

0.0772

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.0432

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.0661

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0601

Hom.:

126

Bravo

AF:

0.0415

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0674

EpiControl

AF:

0.0617

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Polycystic kidney disease, adult type

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 09, 2017	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 22, 2020	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 03, 2019	- -
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

Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

Thec.2730C>T, p.Asp910Asp variant was identified in 5.5% of 6399 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

-0.72

CADD

Benign

0.86

DANN

Benign

0.75

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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