Genetic Variant PKD1L2:p.Val183Ile (chr16-81215111-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/18 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

Publications

26 publications found

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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new If you want to explore the variant's impact on the transcript ENST00000525539.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525539.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	NR_126532.3		n.571G>A		non_coding_transcript_exon	Exon 3 of 43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.547G>A	p.Val183Ile	missense	Exon 3 of 43	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

GnomAD2 exomes

AF:

0.233

AC:

55380

AN:

237516

AF XY:

0.231

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 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

African (AFR)

AF:

0.157

AC:

5252

AN:

33410

American (AMR)

AF:

0.232

AC:

10139

AN:

43660

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

5456

AN:

25962

East Asian (EAS)

AF:

0.386

AC:

15238

AN:

39492

South Asian (SAS)

AF:

0.244

AC:

20752

AN:

85022

European-Finnish (FIN)

AF:

0.283

AC:

14947

AN:

52834

Middle Eastern (MID)

AF:

0.112

AC:

645

AN:

5766

European-Non Finnish (NFE)

AF:

0.220

AC:

243603

AN:

1109532

Other (OTH)

AF:

0.218

AC:

13095

AN:

60158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13626

27253

40879

54506

68132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8570

17140

25710

34280

42850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.209

AC:

31729

AN:

152062

Hom.:

3498

Cov.:

AF XY:

0.211

AC XY:

15646

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.161

AC:

6678

AN:

41478

American (AMR)

AF:

0.195

AC:

2977

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

777

AN:

3470

East Asian (EAS)

AF:

0.368

AC:

1898

AN:

5156

South Asian (SAS)

AF:

0.249

AC:

1201

AN:

4814

European-Finnish (FIN)

AF:

0.271

AC:

2870

AN:

10580

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14729

AN:

67982

Other (OTH)

AF:

0.182

AC:

383

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1274

2548

3823

5097

6371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.211

Hom.:

16185

Bravo

AF:

0.200

Asia WGS

AF:

0.263

AC:

914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.8

(source)

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

PhyloP100

0.56

PrimateAI

Benign

0.29

PROVEAN

Benign

0.41

REVEL

Benign

0.058

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over