rs555901411

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001009944.3(PKD1):c.8110G>A(p.Ala2704Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,590,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2704V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000087 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

PKD1
NM_001009944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.80

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021850973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.8110G>A	p.Ala2704Thr	missense_variant	Exon 22 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.8110G>A	p.Ala2704Thr	missense_variant	Exon 22 of 46	1	NM_001009944.3	ENSP00000262304.4

Frequencies

GnomAD3 genomes

AF:

0.0000867

AC:

AN:

149888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000202

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000485

GnomAD2 exomes

AF:

0.0000318

AC:

AN:

157348

AF XY:

0.0000118

show subpopulations

Gnomad AFR exome

AF:

0.000239

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:

0.0000482

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000285

AC:

AN:

1440706

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

715758

show subpopulations

African (AFR)

AF:

0.0000604

AC:

AN:

33106

American (AMR)

AF:

0.00

AC:

AN:

43112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25736

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39216

South Asian (SAS)

AF:

0.0000119

AC:

AN:

83764

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4110

European-Non Finnish (NFE)

AF:

0.0000317

AC:

AN:

1102592

Other (OTH)

AF:

0.0000168

AC:

AN:

59526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000867

AC:

AN:

150006

Hom.:

Cov.:

AF XY:

0.0000820

AC XY:

AN XY:

73202

show subpopulations

African (AFR)

AF:

0.000247

AC:

AN:

40470

American (AMR)

AF:

0.00

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.000202

AC:

AN:

4948

South Asian (SAS)

AF:

0.00

AC:

AN:

4702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67500

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.0000712

Hom.:

ExAC

AF:

0.0000270

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 11, 2016

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Polycystic kidney disease, adult type

Uncertain:1

Jan 02, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.5

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

LIST_S2

Benign

0.55

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.29

N;N

PhyloP100

1.8

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.35

N;N

Sift

Benign

0.27

T;T

Sift4G

Benign

0.26

T;T

Vest4

0.039

ClinPred

0.020

GERP RS

-3.9

Varity_R

0.022

gMVP

0.10

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over