rs1057518906

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_000297.4(PKD2):c.145C>T(p.Gln49*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000305 in 1,311,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

PKD2
NM_000297.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 1.76

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:

ENSG00000286618 (HGNC:):

ENSG00000286618 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 18 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-88007878-C-T is Pathogenic according to our data. Variant chr4-88007878-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 374110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD2	NM_000297.4 link	c.145C>T	p.Gln49*	stop_gained	Exon 1 of 15	ENST00000237596.7	NP_000288.1	Q13563-1Q9UEU6
PKD2	NM_001440544.1 link	c.145C>T	p.Gln49*	stop_gained	Exon 1 of 14		NP_001427473.1
PKD2	NR_156488.2 link	n.244C>T		non_coding_transcript_exon_variant	Exon 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD2	ENST00000237596.7 link	c.145C>T	p.Gln49*	stop_gained	Exon 1 of 15	1	NM_000297.4	ENSP00000237596.2		Q13563-1
ENSG00000286618	ENST00000662475.1 link	n.112+488G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150548

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000172

AC:

AN:

1161130

Hom.:

Cov.:

AF XY:

0.00000178

AC XY:

AN XY:

560354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24620

American (AMR)

AF:

0.00

AC:

AN:

17632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17298

East Asian (EAS)

AF:

0.00

AC:

AN:

26300

South Asian (SAS)

AF:

0.00

AC:

AN:

41698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3322

European-Non Finnish (NFE)

AF:

0.00000209

AC:

AN:

958400

Other (OTH)

AF:

0.00

AC:

AN:

46572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150548

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41224

American (AMR)

AF:

0.00

AC:

AN:

15112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67566

Other (OTH)

AF:

0.00

AC:

AN:

2078

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

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Polycystic kidney disease

Pathogenic:1

Jun 23, 2015

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic kidney disease 2

Pathogenic:1

Jun 13, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.58

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.48

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.39

PhyloP100

1.8

Vest4

0.57

GERP RS

2.0

PromoterAI

-0.031

Neutral

(source)

Mutation Taster

=2/198

disease causing (ClinVar)

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over