Variant 16-81215111-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.547G>A(p.Val183Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,607,898 control chromosomes in the GnomAD database, including 41,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 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 0.21 ( 3498 hom., cov: 31)

Exomes 𝑓: 0.23 ( 38475 hom. )

Consequence

PKD1L2
ENST00000525539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.559

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:

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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=0.0045801103).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3 link	n.571G>A		non_coding_transcript_exon_variant	3/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5 link	c.547G>A	p.Val183Ile	missense_variant	3/43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31717

AN:

151944

Hom.:

3498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.233

AC:

55380

AN:

237516

Hom.:

6638

AF XY:

0.231

AC XY:

29899

AN XY:

129208

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.226

AC:

329127

AN:

1455836

Hom.:

38475

Cov.:

AF XY:

0.227

AC XY:

163977

AN XY:

723740

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.244

Gnomad4 FIN exome

AF:

0.283

Gnomad4 NFE exome

AF:

0.220

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.209

AC:

31729

AN:

152062

Hom.:

3498

Cov.:

AF XY:

0.211

AC XY:

15646

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.368

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.206

Hom.:

8435

Bravo

AF:

0.200

TwinsUK

AF:

0.220

AC:

816

ALSPAC

AF:

0.216

AC:

832

ESP6500AA

AF:

0.148

AC:

584

ESP6500EA

AF:

0.215

AC:

1779

ExAC

AF:

0.227

AC:

27454

Asia WGS

AF:

0.263

AC:

914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.8

DANN

Benign

0.79

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.29

PROVEAN

Benign

0.41

REVEL

Benign

0.058

Polyphen

0.0010

Vest4

0.030

ClinPred

0.013

GERP RS

-9.5

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