Genetic Variant PKD1L2:p.Gly129Asp (chr16-81216322-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.386G>A(p.Gly129Asp) variant causes a missense change. The variant allele was found at a frequency of 0.298 in 1,613,732 control chromosomes in the GnomAD database, including 78,090 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.

Frequency

Genomes: 𝑓 0.25 ( 5902 hom., cov: 33)

Exomes 𝑓: 0.30 ( 72188 hom. )

Consequence

PKD1L2
ENST00000525539.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.28

Publications

19 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=0.0021229684).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 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.410G>A		non_coding_transcript_exon	Exon 2 of 43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.386G>A	p.Gly129Asp	missense	Exon 2 of 43	ENSP00000434417.1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38478

AN:

152024

Hom.:

5905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.00734

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.301

GnomAD2 exomes

AF:

0.260

AC:

64940

AN:

249314

AF XY:

0.266

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.00590

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.357

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.303

AC:

442269

AN:

1461590

Hom.:

72188

Cov.:

AF XY:

0.301

AC XY:

218840

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.103

AC:

3434

AN:

33478

American (AMR)

AF:

0.186

AC:

8297

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

9825

AN:

26118

East Asian (EAS)

AF:

0.00300

AC:

119

AN:

39700

South Asian (SAS)

AF:

0.155

AC:

13390

AN:

86224

European-Finnish (FIN)

AF:

0.295

AC:

15715

AN:

53354

Middle Eastern (MID)

AF:

0.421

AC:

2428

AN:

5768

European-Non Finnish (NFE)

AF:

0.334

AC:

371854

AN:

1111844

Other (OTH)

AF:

0.285

AC:

17207

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17174

34348

51523

68697

85871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11380

22760

34140

45520

56900

<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:

0.253

AC:

38470

AN:

152142

Hom.:

5902

Cov.:

AF XY:

0.248

AC XY:

18433

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.112

AC:

4649

AN:

41512

American (AMR)

AF:

0.252

AC:

3846

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1254

AN:

3466

East Asian (EAS)

AF:

0.00736

AC:

AN:

5164

South Asian (SAS)

AF:

0.151

AC:

729

AN:

4832

European-Finnish (FIN)

AF:

0.288

AC:

3050

AN:

10596

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.350

AC:

23769

AN:

67966

Other (OTH)

AF:

0.298

AC:

628

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1403

2807

4210

5614

7017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.309

Hom.:

17791

Bravo

AF:

0.244

Asia WGS

AF:

0.0830

AC:

291

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

PhyloP100

4.3

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.28

Mutation Taster

=58/42

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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