rs1477510994

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_000297.4(PKD2):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,050,252 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PKD2
NM_000297.4 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.111

Publications

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

PKD2 links:

ENSG00000286618 (HGNC:):

ENSG00000286618 links:

ENSG00000289034 (HGNC:58844):

ENSG00000289034 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 30 codons. Genomic position: 88007821. Lost 0.030 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKD2	NM_000297.4	MANE Select	c.2T>A	p.Met1?	start_lost	Exon 1 of 15	NP_000288.1	Q13563-1
PKD2	NM_001440544.1		c.2T>A	p.Met1?	start_lost	Exon 1 of 14	NP_001427473.1
PKD2	NR_156488.2		n.101T>A		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKD2	ENST00000237596.7	TSL:1 MANE Select	c.2T>A	p.Met1?	start_lost	Exon 1 of 15	ENSP00000237596.2	Q13563-1
PKD2	ENST00000927447.1		c.2T>A	p.Met1?	start_lost	Exon 1 of 15	ENSP00000597506.1
PKD2	ENST00000927448.1		c.2T>A	p.Met1?	start_lost	Exon 1 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149268

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000362

AC:

AN:

55236

AF XY:

0.0000300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000190

AC:

AN:

1050252

Hom.:

Cov.:

AF XY:

0.00000196

AC XY:

AN XY:

510934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20326

American (AMR)

AF:

0.000141

AC:

AN:

14200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13966

East Asian (EAS)

AF:

0.00

AC:

AN:

14370

South Asian (SAS)

AF:

0.00

AC:

AN:

41100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3044

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

888662

Other (OTH)

AF:

0.00

AC:

AN:

38452

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

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

149268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72804

African (AFR)

AF:

0.00

AC:

AN:

41058

American (AMR)

AF:

0.00

AC:

AN:

15034

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5076

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66956

Other (OTH)

AF:

0.00

AC:

AN:

2056

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant polycystic kidney disease (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.16

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.055

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.96

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.77

PhyloP100

-0.11

PROVEAN

Benign

-0.22

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.084

Vest4

0.55

MutPred

0.99

Gain of glycosylation at S4 (P = 0.0079)

MVP

0.69

ClinPred

0.89

GERP RS

2.7

PromoterAI

-0.091

Neutral

(source)

Varity_R

0.94

gMVP

0.33

Mutation Taster

=81/119

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over