Genetic Variant PKD2:p.Ala190Ala (chr4-88008303-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000297.4(PKD2):c.570G>A(p.Ala190Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A190A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PKD2
NM_000297.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0680

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: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

PKD2 links:

ENSG00000286618 (HGNC:):

ENSG00000286618 links:

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new If you want to explore the variant's impact on the transcript NM_000297.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=-0.068 with no splicing effect.

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.570G>A	p.Ala190Ala	synonymous	Exon 1 of 15	NP_000288.1	Q13563-1
PKD2	NM_001440544.1		c.570G>A	p.Ala190Ala	synonymous	Exon 1 of 14	NP_001427473.1
PKD2	NR_156488.2		n.669G>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.570G>A	p.Ala190Ala	synonymous	Exon 1 of 15	ENSP00000237596.2	Q13563-1
PKD2	ENST00000927447.1		c.570G>A	p.Ala190Ala	synonymous	Exon 1 of 15	ENSP00000597506.1
PKD2	ENST00000927448.1		c.570G>A	p.Ala190Ala	synonymous	Exon 1 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1359456

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670426

African (AFR)

AF:

0.00

AC:

AN:

28884

American (AMR)

AF:

0.00

AC:

AN:

33490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24548

East Asian (EAS)

AF:

0.00

AC:

AN:

33760

South Asian (SAS)

AF:

0.00

AC:

AN:

76484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4000

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068326

Other (OTH)

AF:

0.00

AC:

AN:

56704

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

-0.068

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over