Variant 10-100291357-G-A 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.1951C>T(p.Arg651Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 1,613,910 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

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=0.0039155185).

BP6

Variant 10-100291357-G-A is Benign according to our data. Variant chr10-100291357-G-A is described in ClinVar as [Benign]. Clinvar id is 734157.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 400 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2L1	NM_016112.3 linkuse as main transcript	c.1951C>T	p.Arg651Cys	missense_variant	12/16	ENST00000318222.4
PKD2L1	NM_001253837.2 linkuse as main transcript	c.1810C>T	p.Arg604Cys	missense_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2L1	ENST00000318222.4 linkuse as main transcript	c.1951C>T	p.Arg651Cys	missense_variant	12/16	1	NM_016112.3	P1	Q9P0L9-1
PKD2L1	ENST00000528248.1 linkuse as main transcript	c.*1691C>T		3_prime_UTR_variant, NMD_transcript_variant	12/16	1
PKD2L1	ENST00000465680.2 linkuse as main transcript	c.105-2879C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00897

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000760

AC:

191

AN:

251444

Hom.:

AF XY:

0.000633

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00941

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000302

AC:

441

AN:

1461754

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

199

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00968

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

152156

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00894

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000546

Hom.:

Bravo

AF:

0.00298

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00102

AC:

124

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Feb 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.30

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.95

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.16

Sift

Benign

0.12

Sift4G

Benign

0.071

Polyphen

0.015

Vest4

0.097

MVP

0.29

MPC

0.091

ClinPred

0.012

GERP RS

-3.1

Varity_R

0.094

gMVP

0.22

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