rs375408086

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_001009944.3(PKD1):c.8118C>T(p.Thr2706Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00056 in 1,580,882 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 0.00037 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00058 ( 0 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.33

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant polycystic kidney disease
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
polycystic kidney disease 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
autosomal recessive polycystic kidney disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Caroli disease
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

PKD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-2104541-G-A is Benign according to our data. Variant chr16-2104541-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 433986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.34 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000579 (829/1430936) while in subpopulation NFE AF = 0.000657 (721/1096740). AF 95% confidence interval is 0.000617. There are 0 homozygotes in GnomAdExome4. There are 404 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.8118C>T	p.Thr2706Thr	synonymous	Exon 22 of 46	NP_001009944.3
	PKD1	NM_000296.4		c.8118C>T	p.Thr2706Thr	synonymous	Exon 22 of 46	NP_000287.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PKD1	ENST00000262304.9	TSL:1 MANE Select	c.8118C>T	p.Thr2706Thr	synonymous	Exon 22 of 46	ENSP00000262304.4
PKD1	ENST00000423118.5	TSL:1	c.8118C>T	p.Thr2706Thr	synonymous	Exon 22 of 46	ENSP00000399501.1
PKD1	ENST00000567946.1	TSL:5	c.177C>T	p.Thr59Thr	synonymous	Exon 2 of 12	ENSP00000457984.1

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

149828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000403

Gnomad SAS

AF:

0.000850

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000563

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000463

AC:

AN:

153352

AF XY:

0.000495

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.0000792

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000851

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000579

AC:

829

AN:

1430936

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

404

AN XY:

710478

show subpopulations

African (AFR)

AF:

0.000304

AC:

AN:

32870

American (AMR)

AF:

0.000238

AC:

AN:

41980

Ashkenazi Jewish (ASJ)

AF:

0.000117

AC:

AN:

25608

East Asian (EAS)

AF:

0.000540

AC:

AN:

38856

South Asian (SAS)

AF:

0.000314

AC:

AN:

82902

European-Finnish (FIN)

AF:

0.000287

AC:

AN:

48760

Middle Eastern (MID)

AF:

0.000244

AC:

AN:

4096

European-Non Finnish (NFE)

AF:

0.000657

AC:

721

AN:

1096740

Other (OTH)

AF:

0.000389

AC:

AN:

59124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000373

AC:

AN:

149946

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

AN XY:

73202

show subpopulations

African (AFR)

AF:

0.000248

AC:

AN:

40378

American (AMR)

AF:

0.0000661

AC:

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.000404

AC:

AN:

4952

South Asian (SAS)

AF:

0.000850

AC:

AN:

4704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000563

AC:

AN:

67520

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000442

Hom.:

Bravo

AF:

0.000393

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (1)

PKD1-related disorder (1)

Polycystic kidney disease, adult type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.75

(source)

DANN

Benign

0.83

PhyloP100

-3.3

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over