Variant 10-100288451-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016112.3(PKD2L1):c.2363C>A(p.Ala788Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 1,609,924 control chromosomes in the GnomAD database, including 2,372 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 0.062 ( 337 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2035 hom. )

Consequence

PKD2L1
NM_016112.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.574

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016729236).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0925 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.2363C>A	p.Ala788Asp	missense_variant	16/16	ENST00000318222.4
PKD2L1	NM_001253837.2 linkuse as main transcript	c.2222C>A	p.Ala741Asp	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2L1	ENST00000318222.4 linkuse as main transcript	c.2363C>A	p.Ala788Asp	missense_variant	16/16	1	NM_016112.3	P1	Q9P0L9-1
PKD2L1	ENST00000528248.1 linkuse as main transcript	c.*2103C>A		3_prime_UTR_variant, NMD_transcript_variant	16/16	1
PKD2L1	ENST00000465680.2 linkuse as main transcript	c.134C>A	p.Ala45Asp	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0624

AC:

9489

AN:

152050

Hom.:

337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.0738

Gnomad AMR

AF:

0.0493

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.0557

Gnomad SAS

AF:

0.0646

Gnomad FIN

AF:

0.0556

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0470

Gnomad OTH

AF:

0.0665

GnomAD3 exomes

AF:

0.0516

AC:

12947

AN:

251146

Hom.:

375

AF XY:

0.0509

AC XY:

6904

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.0982

Gnomad AMR exome

AF:

0.0450

Gnomad ASJ exome

AF:

0.0559

Gnomad EAS exome

AF:

0.0523

Gnomad SAS exome

AF:

0.0617

Gnomad FIN exome

AF:

0.0496

Gnomad NFE exome

AF:

0.0441

Gnomad OTH exome

AF:

0.0502

GnomAD4 exome

AF:

0.0499

AC:

72748

AN:

1457756

Hom.:

2035

Cov.:

AF XY:

0.0498

AC XY:

36114

AN XY:

725462

show subpopulations

Gnomad4 AFR exome

AF:

0.0960

Gnomad4 AMR exome

AF:

0.0456

Gnomad4 ASJ exome

AF:

0.0544

Gnomad4 EAS exome

AF:

0.0645

Gnomad4 SAS exome

AF:

0.0576

Gnomad4 FIN exome

AF:

0.0517

Gnomad4 NFE exome

AF:

0.0470

Gnomad4 OTH exome

AF:

0.0571

GnomAD4 genome

AF:

0.0624

AC:

9496

AN:

152168

Hom.:

337

Cov.:

AF XY:

0.0627

AC XY:

4662

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0950

Gnomad4 AMR

AF:

0.0493

Gnomad4 ASJ

AF:

0.0565

Gnomad4 EAS

AF:

0.0560

Gnomad4 SAS

AF:

0.0645

Gnomad4 FIN

AF:

0.0556

Gnomad4 NFE

AF:

0.0470

Gnomad4 OTH

AF:

0.0658

Alfa

AF:

0.0469

Hom.:

316

Bravo

AF:

0.0634

TwinsUK

AF:

0.0450

AC:

167

ALSPAC

AF:

0.0472

AC:

182

ESP6500AA

AF:

0.0940

AC:

414

ESP6500EA

AF:

0.0462

AC:

397

ExAC

AF:

0.0524

AC:

6364

EpiCase

AF:

0.0440

EpiControl

AF:

0.0436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.4

DANN

Benign

0.68

DEOGEN2

Benign

0.014

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.68

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Benign

0.23

Polyphen

0.0010

Vest4

0.038

MPC

0.33

ClinPred

0.075

GERP RS

-1.1

Varity_R

0.26

gMVP

0.44

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over