Variant 16-81175642-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000525539.5(PKD1L2):c.2546G>A(p.Arg849His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 1,613,926 control chromosomes in the GnomAD database, including 1,003 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.026 ( 75 hom., cov: 32)

Exomes 𝑓: 0.033 ( 928 hom. )

Consequence

PKD1L2
ENST00000525539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.47

Variant links:

Genes affected

PKD1L2 (HGNC:21715): (polycystin 1 like 2 (gene/pseudogene)) This gene encodes a member of the polycystin protein family. This protein may function as a G-protein-coupled component or regulator of cation channel pores. The long isoform of this protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene is a polymorphic pseudogene in humans. [provided by RefSeq, May 2022]

PKD1L2 links:

PKD1L2 (HGNC:):

PKD1L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00234133).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3 linkuse as main transcript	n.2561G>A		non_coding_transcript_exon_variant	15/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5 linkuse as main transcript	c.2546G>A	p.Arg849His	missense_variant	15/43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3884

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00623

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0300

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0370

Gnomad OTH

AF:

0.0320

GnomAD3 exomes

AF:

0.0273

AC:

6806

AN:

249574

Hom.:

127

AF XY:

0.0291

AC XY:

3937

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.00530

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0424

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0264

Gnomad FIN exome

AF:

0.0281

Gnomad NFE exome

AF:

0.0367

Gnomad OTH exome

AF:

0.0346

GnomAD4 exome

AF:

0.0331

AC:

48386

AN:

1461644

Hom.:

928

Cov.:

AF XY:

0.0337

AC XY:

24469

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00606

Gnomad4 AMR exome

AF:

0.0160

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0276

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.0363

Gnomad4 OTH exome

AF:

0.0304

GnomAD4 genome

AF:

0.0255

AC:

3884

AN:

152282

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1872

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00623

Gnomad4 AMR

AF:

0.0252

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0303

Gnomad4 FIN

AF:

0.0273

Gnomad4 NFE

AF:

0.0370

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0341

Hom.:

230

Bravo

AF:

0.0247

TwinsUK

AF:

0.0386

AC:

143

ALSPAC

AF:

0.0350

AC:

135

ESP6500AA

AF:

0.00758

AC:

ESP6500EA

AF:

0.0361

AC:

304

ExAC

AF:

0.0276

AC:

3341

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.11

DANN

Benign

0.85

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.041

Polyphen

0.015, 0.0020

.;B;B

Vest4

0.071

MPC

.;.;5.55450975E-4

ClinPred

0.00081

GERP RS

-8.1

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