dbSNP rs62310565: PKD2:c.596-16C>A (chr4-88019442-C-A) – 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.596-16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000936 in 1,068,418 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: not found (cov: 32)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

PKD2
NM_000297.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.918

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:

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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=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PKD2	NM_000297.4 link	c.596-16C>A	intron_variant	Intron 1 of 14	ENST00000237596.7	NP_000288.1	Q13563-1Q9UEU6
PKD2	NM_001440544.1 link	c.596-16C>A	intron_variant	Intron 1 of 13		NP_001427473.1
PKD2	NR_156488.2 link	n.695-16C>A	intron_variant	Intron 1 of 13
PKD2	XM_011532029.2 link	c.-197C>A	upstream_gene_variant			XP_011530331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD2	ENST00000237596.7 link	c.596-16C>A		intron_variant	Intron 1 of 14	1	NM_000297.4	ENSP00000237596.2		Q13563-1
PKD2	ENST00000506727.1 link	n.98-16C>A		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.36e-7

AC:

AN:

1068418

Hom.:

Cov.:

AF XY:

0.00000182

AC XY:

AN XY:

549970

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25494

American (AMR)

AF:

0.00

AC:

AN:

44002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23678

East Asian (EAS)

AF:

0.00

AC:

AN:

37494

South Asian (SAS)

AF:

0.00

AC:

AN:

77366

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4952

European-Non Finnish (NFE)

AF:

0.00000132

AC:

AN:

755028

Other (OTH)

AF:

0.00

AC:

AN:

47364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.3

(source)

DANN

Benign

0.63

PhyloP100

-0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over