rs2855349

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001009944.3(PKD1):c.2986-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,595,606 control chromosomes in the GnomAD database, including 2,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 249 hom., cov: 32)

Exomes 𝑓: 0.030 ( 2505 hom. )

Consequence

PKD1
NM_001009944.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.570

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 16-2112978-G-A is Benign according to our data. Variant chr16-2112978-G-A is described in ClinVar as [Benign]. Clinvar id is 256939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2112978-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.2986-15C>T		intron_variant	Intron 12 of 45	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.2986-15C>T		intron_variant	Intron 12 of 45	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4461

AN:

152204

Hom.:

242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0309

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0553

AC:

13227

AN:

239304

Hom.:

1054

AF XY:

0.0594

AC XY:

7758

AN XY:

130648

show subpopulations

Gnomad AFR exome

AF:

0.0221

Gnomad AMR exome

AF:

0.0435

Gnomad ASJ exome

AF:

0.0143

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.00657

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0388

GnomAD4 exome

AF:

0.0296

AC:

42663

AN:

1443284

Hom.:

2505

Cov.:

AF XY:

0.0331

AC XY:

23798

AN XY:

718578

show subpopulations

Gnomad4 AFR exome

AF:

0.0232

Gnomad4 AMR exome

AF:

0.0430

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.162

Gnomad4 FIN exome

AF:

0.00701

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.0426

GnomAD4 genome

AF:

0.0294

AC:

4482

AN:

152322

Hom.:

249

Cov.:

AF XY:

0.0321

AC XY:

2393

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.0311

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.00612

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.00826

Hom.:

Bravo

AF:

0.0291

Asia WGS

AF:

0.234

AC:

813

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease, adult type

Benign:1

Feb 20, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.2986-15C>T, p.? variant was identified in 5.3% of 6391 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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.025

DANN

Benign

0.72

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

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