Genetic Variant PKD2L1:c.2336-34C>T (chr10-100288512-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016112.3(PKD2L1):c.2336-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 1,306,946 control chromosomes in the GnomAD database, including 1,692 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 0.063 ( 340 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1352 hom. )

Consequence

PKD2L1
NM_016112.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.821

Publications

10 publications found

Variant links:

Genes affected

PKD2L1 (HGNC:9011): (polycystin 2 like 1, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

PKD2L1 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD2L1	NM_016112.3 link	c.2336-34C>T		intron_variant	Intron 15 of 15	ENST00000318222.4	NP_057196.2	Q9P0L9-1
PKD2L1	NM_001253837.2 link	c.2195-34C>T		intron_variant	Intron 15 of 15		NP_001240766.1	Q9P0L9Q1L4F0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PKD2L1	ENST00000318222.4 link	c.2336-34C>T	intron_variant	Intron 15 of 15	1	NM_016112.3	ENSP00000325296.3	Q9P0L9-1
PKD2L1	ENST00000528248.1 link	n.*2076-34C>T	intron_variant	Intron 15 of 15	1		ENSP00000436514.1	H0YET4
PKD2L1	ENST00000465680.2 link	c.104-34C>T	intron_variant	Intron 1 of 1	3		ENSP00000434019.1	H0YDN7

Frequencies

GnomAD3 genomes

AF:

0.0627

AC:

9532

AN:

152058

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.0491

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0554

Gnomad SAS

AF:

0.0644

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0472

Gnomad OTH

AF:

0.0670

GnomAD2 exomes

AF:

0.0517

AC:

12820

AN:

248012

AF XY:

0.0511

show subpopulations

Gnomad AFR exome

AF:

0.0976

Gnomad AMR exome

AF:

0.0445

Gnomad ASJ exome

AF:

0.0636

Gnomad EAS exome

AF:

0.0521

Gnomad FIN exome

AF:

0.0494

Gnomad NFE exome

AF:

0.0440

Gnomad OTH exome

AF:

0.0506

GnomAD4 exome

AF:

0.0459

AC:

52975

AN:

1154770

Hom.:

1352

Cov.:

AF XY:

0.0463

AC XY:

27289

AN XY:

589194

show subpopulations

African (AFR)

AF:

0.0897

AC:

2445

AN:

27250

American (AMR)

AF:

0.0451

AC:

1992

AN:

44168

Ashkenazi Jewish (ASJ)

AF:

0.0605

AC:

1466

AN:

24228

East Asian (EAS)

AF:

0.0643

AC:

2466

AN:

38352

South Asian (SAS)

AF:

0.0564

AC:

4512

AN:

79998

European-Finnish (FIN)

AF:

0.0515

AC:

2730

AN:

53052

Middle Eastern (MID)

AF:

0.0473

AC:

248

AN:

5238

European-Non Finnish (NFE)

AF:

0.0413

AC:

34411

AN:

832334

Other (OTH)

AF:

0.0539

AC:

2705

AN:

50150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

2127

4255

6382

8510

10637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1152

2304

3456

4608

5760

<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:

0.0627

AC:

9539

AN:

152176

Hom.:

340

Cov.:

AF XY:

0.0630

AC XY:

4689

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0950

AC:

3947

AN:

41526

American (AMR)

AF:

0.0491

AC:

751

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3468

East Asian (EAS)

AF:

0.0557

AC:

288

AN:

5170

South Asian (SAS)

AF:

0.0642

AC:

309

AN:

4812

European-Finnish (FIN)

AF:

0.0557

AC:

590

AN:

10592

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0472

AC:

3209

AN:

68012

Other (OTH)

AF:

0.0663

AC:

140

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

460

921

1381

1842

2302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0565

Hom.:

Bravo

AF:

0.0636

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.3

(source)

DANN

Benign

0.46

PhyloP100

0.82

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over