dbSNP rs371898195: PKD2:p.Gly121Arg (chr4-88008094-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000297.4(PKD2):c.361G>C(p.Gly121Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000732 in 1,365,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G121C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

PKD2
NM_000297.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.76

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34659255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PKD2	NM_000297.4 link	c.361G>C	p.Gly121Arg	missense_variant	Exon 1 of 15	ENST00000237596.7	NP_000288.1
PKD2	NM_001440544.1 link	c.361G>C	p.Gly121Arg	missense_variant	Exon 1 of 14		NP_001427473.1
PKD2	NR_156488.2 link	n.460G>C		non_coding_transcript_exon_variant	Exon 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PKD2	ENST00000237596.7 link	c.361G>C	p.Gly121Arg	missense_variant	Exon 1 of 15	1	NM_000297.4	ENSP00000237596.2
ENSG00000286618	ENST00000662475.1 link	n.112+272C>G		intron_variant	Intron 1 of 2
PKD2	ENST00000506727.1 link	n.-138G>C		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.32e-7

AC:

AN:

1365346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29680

American (AMR)

AF:

0.00

AC:

AN:

33678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24642

East Asian (EAS)

AF:

0.00

AC:

AN:

33944

South Asian (SAS)

AF:

0.00

AC:

AN:

77158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5496

European-Non Finnish (NFE)

AF:

9.35e-7

AC:

AN:

1069908

Other (OTH)

AF:

0.00

AC:

AN:

57062

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.81

PhyloP100

5.8

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.48

REVEL

Benign

0.11

Sift

Benign

0.040

Sift4G

Benign

0.18

Polyphen

0.91

Vest4

0.36

MutPred

0.14

Gain of glycosylation at S125 (P = 0.0163);

MVP

0.31

MPC

0.71

ClinPred

0.86

GERP RS

3.5

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.22

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

Other links and lift over