Variant chr16-2099852-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_001009944.3(PKD1):c.9923+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,563,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

PKD1
NM_001009944.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.138

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 16-2099852-G-A is Benign according to our data. Variant chr16-2099852-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257046.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1	NM_001009944.3 linkuse as main transcript	c.9923+9C>T		intron_variant		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.9923+9C>T		intron_variant		1	NM_001009944.3	ENSP00000262304	P5	P98161-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

167580

Hom.:

AF XY:

0.0000782

AC XY:

AN XY:

89568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000817

Gnomad SAS exome

AF:

0.000126

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.000216

GnomAD4 exome

AF:

0.0000503

AC:

AN:

1411476

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

697924

show subpopulations

Gnomad4 AFR exome

AF:

0.000186

Gnomad4 AMR exome

AF:

0.0000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000619

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.000222

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.7

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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