Variant rs7205673 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.1535C>T(p.Pro512Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,613,156 control chromosomes in the GnomAD database, including 502,089 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P512T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.76 ( 44155 hom., cov: 32)

Exomes 𝑓: 0.79 ( 457934 hom. )

Consequence

PKD1L2
ENST00000525539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

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=9.383563E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L2	NR_126532.3 linkuse as main transcript	n.1550C>T		non_coding_transcript_exon_variant	7/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL
PKD1L2	ENST00000525539.5 linkuse as main transcript	c.1535C>T	p.Pro512Leu	missense_variant	7/43	1
PKD1L2	ENST00000526632.5 linkuse as main transcript	c.119C>T	p.Pro40Leu	missense_variant	1/12	2
PKD1L2	ENST00000710634.1 linkuse as main transcript	c.152C>T	p.Pro51Leu	missense_variant, NMD_transcript_variant	1/10

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115111

AN:

151952

Hom.:

44148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.656

Gnomad AMI

AF:

0.800

Gnomad AMR

AF:

0.770

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.959

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.829

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.742

GnomAD3 exomes

AF:

0.791

AC:

196561

AN:

248588

Hom.:

78365

AF XY:

0.790

AC XY:

106486

AN XY:

134874

show subpopulations

Gnomad AFR exome

AF:

0.644

Gnomad AMR exome

AF:

0.795

Gnomad ASJ exome

AF:

0.786

Gnomad EAS exome

AF:

0.958

Gnomad SAS exome

AF:

0.724

Gnomad FIN exome

AF:

0.829

Gnomad NFE exome

AF:

0.794

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.790

AC:

1154960

AN:

1461086

Hom.:

457934

Cov.:

AF XY:

0.789

AC XY:

573524

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.649

Gnomad4 AMR exome

AF:

0.794

Gnomad4 ASJ exome

AF:

0.779

Gnomad4 EAS exome

AF:

0.959

Gnomad4 SAS exome

AF:

0.727

Gnomad4 FIN exome

AF:

0.829

Gnomad4 NFE exome

AF:

0.793

Gnomad4 OTH exome

AF:

0.780

GnomAD4 genome

AF:

0.757

AC:

115148

AN:

152070

Hom.:

44155

Cov.:

AF XY:

0.760

AC XY:

56497

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.771

Gnomad4 ASJ

AF:

0.775

Gnomad4 EAS

AF:

0.959

Gnomad4 SAS

AF:

0.719

Gnomad4 FIN

AF:

0.829

Gnomad4 NFE

AF:

0.791

Gnomad4 OTH

AF:

0.737

Alfa

AF:

0.791

Hom.:

106592

Bravo

AF:

0.754

TwinsUK

AF:

0.797

AC:

2955

ALSPAC

AF:

0.789

AC:

3040

ESP6500AA

AF:

0.664

AC:

2650

ESP6500EA

AF:

0.793

AC:

6579

ExAC

AF:

0.786

AC:

95012

Asia WGS

AF:

0.809

AC:

2812

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.53

MetaRNN

Benign

9.4e-7

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.40

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.22

Polyphen

1.0

Vest4

0.40

ClinPred

0.048

GERP RS

5.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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