dbSNP rs2728111: PKD2:c.710-5236C>T (chr4-88030984-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 NM_000297.4(PKD2):c.710-5236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,254 control chromosomes in the GnomAD database, including 49,967 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 0.81 ( 49967 hom., cov: 33)

Consequence

PKD2
NM_000297.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.65

Publications

1 publications found

Variant links:

Genes affected

PKD2 (HGNC:9009): (polycystin 2, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein is a multi-pass membrane protein that functions as a calcium permeable cation channel, and is involved in calcium transport and calcium signaling in renal epithelial cells. This protein interacts with polycystin 1, and they may be partners in a common signaling cascade involved in tubular morphogenesis. Mutations in this gene are associated with autosomal dominant polycystic kidney disease type 2. [provided by RefSeq, Mar 2011]

PKD2 Gene-Disease associations (from GenCC):

autosomal dominant polycystic kidney disease
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
polycystic kidney disease 2
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

PKD2 links:

Genome browser will be placed here

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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PKD2	NM_000297.4 link	c.710-5236C>T	intron_variant	Intron 2 of 14	ENST00000237596.7	NP_000288.1
PKD2	NM_001440544.1 link	c.710-5236C>T	intron_variant	Intron 2 of 13		NP_001427473.1
PKD2	NR_156488.2 link	n.809-5236C>T	intron_variant	Intron 2 of 13
PKD2	XM_011532029.2 link	c.-67-101C>T	intron_variant	Intron 1 of 14		XP_011530331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD2	ENST00000237596.7 link	c.710-5236C>T		intron_variant	Intron 2 of 14	1	NM_000297.4	ENSP00000237596.2
PKD2	ENST00000506727.1 link	n.212-5152C>T		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122777

AN:

152136

Hom.:

49919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.909

Gnomad AMI

AF:

0.824

Gnomad AMR

AF:

0.772

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.811

Gnomad FIN

AF:

0.833

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.762

Gnomad OTH

AF:

0.766

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.807

AC:

122881

AN:

152254

Hom.:

49967

Cov.:

AF XY:

0.810

AC XY:

60331

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.909

AC:

37771

AN:

41564

American (AMR)

AF:

0.772

AC:

11810

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.710

AC:

2462

AN:

3468

East Asian (EAS)

AF:

0.714

AC:

3694

AN:

5172

South Asian (SAS)

AF:

0.810

AC:

3908

AN:

4826

European-Finnish (FIN)

AF:

0.833

AC:

8833

AN:

10600

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.762

AC:

51840

AN:

68012

Other (OTH)

AF:

0.766

AC:

1620

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1216

2433

3649

4866

6082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.786

Hom.:

18050

Bravo

AF:

0.807

Asia WGS

AF:

0.778

AC:

2703

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.32

(source)

DANN

Benign

0.72

PhyloP100

-2.6

Mutation Taster

=100/0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over