16-2094108-C-T

Variant names:

• chr16-2094108-C-T
• rs572474052
• NM_001009944.3:c.10602G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001009944.3(PKD1):​c.10602G>A​(p.Ala3534Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000634 in 1,592,112 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 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: PKD1 NM_001009944.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:4
• Conservation: PhyloP100: -1.46
• Publications: 2 publications found

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-AS1 (HGNC:56035): (PKD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-2094108-C-T is Benign according to our data. Variant chr16-2094108-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 586241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.46 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3	c.10602G>A	p.Ala3534Ala	synonymous_variant	Exon 35 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9	c.10602G>A	p.Ala3534Ala	synonymous_variant	Exon 35 of 46	1	NM_001009944.3	ENSP00000262304.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000334 AC: 7 AN: 209888 AF XY: 0.0000438

Gnomad AFR exome AF: 0.0000797

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000556

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000674 AC: 97 AN: 1439782 Hom.: 0 Cov.: 30 AF XY: 0.0000798 AC XY: 57 AN XY: 714544

African (AFR) AF: 0.0000604 AC: 2 AN: 33094

American (AMR) AF: 0.00 AC: 0 AN: 42058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25662

East Asian (EAS) AF: 0.00 AC: 0 AN: 38770

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000827 AC: 91 AN: 1100866

Other (OTH) AF: 0.0000336 AC: 2 AN: 59564

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74476

African (AFR) AF: 0.0000241 AC: 1 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:4

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 12, 2018

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.77
DANN	Benign	0.85
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs572474052; hg19: chr16-2144109;