Variant rs6584356 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016112.3(PKD2L1):c.2042G>T(p.Arg681Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0605 in 1,612,512 control chromosomes in the GnomAD database, including 3,293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.069 ( 403 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2890 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2L1	NM_016112.3 linkuse as main transcript	c.2042G>T	p.Arg681Leu	missense_variant	13/16	ENST00000318222.4
PKD2L1	NM_001253837.2 linkuse as main transcript	c.1901G>T	p.Arg634Leu	missense_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2L1	ENST00000318222.4 linkuse as main transcript	c.2042G>T	p.Arg681Leu	missense_variant	13/16	1	NM_016112.3	P1	Q9P0L9-1
PKD2L1	ENST00000528248.1 linkuse as main transcript	c.*1782G>T		3_prime_UTR_variant, NMD_transcript_variant	13/16	1
PKD2L1	ENST00000465680.2 linkuse as main transcript	c.105-2007G>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0690

AC:

10491

AN:

152124

Hom.:

403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0994

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0554

Gnomad ASJ

AF:

0.0662

Gnomad EAS

AF:

0.0560

Gnomad SAS

AF:

0.0710

Gnomad FIN

AF:

0.0615

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0556

Gnomad OTH

AF:

0.0731

GnomAD3 exomes

AF:

0.0583

AC:

14594

AN:

250460

Hom.:

483

AF XY:

0.0578

AC XY:

7826

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.0512

Gnomad ASJ exome

AF:

0.0653

Gnomad EAS exome

AF:

0.0524

Gnomad SAS exome

AF:

0.0680

Gnomad FIN exome

AF:

0.0554

Gnomad NFE exome

AF:

0.0522

Gnomad OTH exome

AF:

0.0607

GnomAD4 exome

AF:

0.0597

AC:

87127

AN:

1460270

Hom.:

2890

Cov.:

AF XY:

0.0595

AC XY:

43205

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.0521

Gnomad4 ASJ exome

AF:

0.0627

Gnomad4 EAS exome

AF:

0.0645

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.0579

Gnomad4 NFE exome

AF:

0.0577

Gnomad4 OTH exome

AF:

0.0674

GnomAD4 genome

AF:

0.0690

AC:

10498

AN:

152242

Hom.:

403

Cov.:

AF XY:

0.0691

AC XY:

5147

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0993

Gnomad4 AMR

AF:

0.0554

Gnomad4 ASJ

AF:

0.0662

Gnomad4 EAS

AF:

0.0563

Gnomad4 SAS

AF:

0.0708

Gnomad4 FIN

AF:

0.0615

Gnomad4 NFE

AF:

0.0556

Gnomad4 OTH

AF:

0.0724

Alfa

AF:

0.0548

Hom.:

629

Bravo

AF:

0.0701

TwinsUK

AF:

0.0572

AC:

212

ALSPAC

AF:

0.0568

AC:

219

ESP6500AA

AF:

0.0980

AC:

432

ESP6500EA

AF:

0.0549

AC:

472

ExAC

AF:

0.0591

AC:

7173

Asia WGS

AF:

0.0850

AC:

297

AN:

3478

EpiCase

AF:

0.0519

EpiControl

AF:

0.0514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.42

DANN

Uncertain

0.98

DEOGEN2

Benign

0.35

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.18

Sift

Uncertain

0.013

Sift4G

Uncertain

0.019

Polyphen

0.046

Vest4

0.056

MPC

0.087

ClinPred

0.045

GERP RS

-6.2

Varity_R

0.11

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: 34

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over