Variant 10-100288427-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016112.3(PKD2L1):c.2387G>A(p.Arg796His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,612,830 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 23 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.74

Variant links:

Genes affected

PKD2L1 (HGNC:9011): (polycystin 2 like 1, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

PKD2L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033938587).

BP6

Variant 10-100288427-C-T is Benign according to our data. Variant chr10-100288427-C-T is described in ClinVar as [Benign]. Clinvar id is 720318.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 166 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2L1	NM_016112.3 linkuse as main transcript	c.2387G>A	p.Arg796His	missense_variant	16/16	ENST00000318222.4
PKD2L1	NM_001253837.2 linkuse as main transcript	c.2246G>A	p.Arg749His	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2L1	ENST00000318222.4 linkuse as main transcript	c.2387G>A	p.Arg796His	missense_variant	16/16	1	NM_016112.3	P1	Q9P0L9-1
PKD2L1	ENST00000528248.1 linkuse as main transcript	c.*2127G>A		3_prime_UTR_variant, NMD_transcript_variant	16/16	1
PKD2L1	ENST00000465680.2 linkuse as main transcript	c.158G>A	p.Arg53His	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00232

AC:

582

AN:

251344

Hom.:

AF XY:

0.00308

AC XY:

418

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00142

AC:

2077

AN:

1460534

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

1349

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000617

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152296

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000929

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00237

AC:

288

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00166

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

Cadd

Benign

0.17

Dann

Benign

0.60

DEOGEN2

Benign

0.083

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.3

REVEL

Benign

0.075

Sift

Benign

0.55

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.014

MVP

0.26

MPC

0.082

ClinPred

0.011

GERP RS

-6.6

Varity_R

0.024

gMVP

0.23

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