Genetic Variant PKD1L2:c.6483+734A>G (chr16-81122917-T-C) – 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.6483+734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,114 control chromosomes in the GnomAD database, including 17,380 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 0.46 ( 17377 hom., cov: 33)

Exomes 𝑓: 0.58 ( 3 hom. )

Consequence

PKD1L2
ENST00000525539.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.879

Publications

9 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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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 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.6498+734A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PKD1L2	ENST00000525539.5	TSL:1	c.6483+734A>G	intron	N/A	ENSP00000434417.1
PKD1L2	ENST00000533478.5	TSL:1	c.4428+734A>G	intron	N/A	ENSP00000434644.1
PKD1L2	ENST00000534142.5	TSL:2	n.872+734A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69381

AN:

151984

Hom.:

17365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.583

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.456

AC:

69401

AN:

152102

Hom.:

17377

Cov.:

AF XY:

0.457

AC XY:

33956

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.236

AC:

9795

AN:

41482

American (AMR)

AF:

0.514

AC:

7849

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1823

AN:

3472

East Asian (EAS)

AF:

0.388

AC:

2010

AN:

5176

South Asian (SAS)

AF:

0.516

AC:

2484

AN:

4816

European-Finnish (FIN)

AF:

0.523

AC:

5529

AN:

10580

Middle Eastern (MID)

AF:

0.445

AC:

129

AN:

290

European-Non Finnish (NFE)

AF:

0.562

AC:

38221

AN:

67994

Other (OTH)

AF:

0.482

AC:

1018

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1844

3688

5532

7376

9220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.495

Hom.:

28252

Bravo

AF:

0.445

Asia WGS

AF:

0.431

AC:

1502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.9

(source)

DANN

Benign

0.60

PhyloP100

0.88

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

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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