Genetic Variant PKD2:c.-82G>T (chr4-88007652-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000297.4(PKD2):c.-82G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 150,812 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.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PKD2
NM_000297.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389

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: 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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	Effect	Exon Rank	Protein	UniProt
PKD2	NM_000297.4	MANE Select	c.-82G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_000288.1	Q13563-1
PKD2	NM_000297.4	MANE Select	c.-82G>T	5_prime_UTR	Exon 1 of 15	NP_000288.1	Q13563-1
PKD2	NM_001440544.1		c.-82G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001427473.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PKD2	ENST00000237596.7	TSL:1 MANE Select	c.-82G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000237596.2	Q13563-1
PKD2	ENST00000237596.7	TSL:1 MANE Select	c.-82G>T	5_prime_UTR	Exon 1 of 15	ENSP00000237596.2	Q13563-1
PKD2	ENST00000927447.1		c.-82G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000597506.1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

790726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

374122

African (AFR)

AF:

0.00

AC:

AN:

14920

American (AMR)

AF:

0.00

AC:

AN:

2670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6202

East Asian (EAS)

AF:

0.00

AC:

AN:

7978

South Asian (SAS)

AF:

0.00

AC:

AN:

17554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

704660

Other (OTH)

AF:

0.00

AC:

AN:

27464

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150812

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73650

show subpopulations

African (AFR)

AF:

0.0000726

AC:

AN:

41294

American (AMR)

AF:

0.00

AC:

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67534

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.39

PromoterAI

-0.18

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over