rs1057518797

Variant names:

• chr4-88008090-CCCGGGCA-TAGGACG
• rs1057518797
• NM_000297.4:c.357_364delCCCGGGCAinsTAGGACG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000297.4(PKD2):​c.357_364delCCCGGGCAinsTAGGACG​(p.Pro120ArgfsTer12) variant causes a frameshift, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PKD2 NM_000297.4 frameshift, missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 5.76
• Publications: 0 publications found

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

ENSG00000286618 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-88008090-CCCGGGCA-TAGGACG is Pathogenic according to our data. Variant chr4-88008090-CCCGGGCA-TAGGACG is described in ClinVar as Pathogenic. ClinVar VariationId is 373955.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	NM_000297.4	MANE Select	c.357_364delCCCGGGCAinsTAGGACG	p.Pro120ArgfsTer12	frameshift missense	Exon 1 of 15	NP_000288.1
	PKD2	NM_001440544.1		c.357_364delCCCGGGCAinsTAGGACG	p.Pro120ArgfsTer12	frameshift missense	Exon 1 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.456_463delCCCGGGCAinsTAGGACG		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.357_364delCCCGGGCAinsTAGGACG	p.Pro120ArgfsTer12	frameshift missense	Exon 1 of 15	ENSP00000237596.2
	ENSG00000286618	ENST00000662475.1		n.112+269_112+276delTGCCCGGGinsCGTCCTA		intron	N/A
	PKD2	ENST00000506727.1	TSL:4	n.-142_-135delCCCGGGCAinsTAGGACG		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Hypertensive disorder;C0022680:Polycystic kidney disease;C1561643:Chronic kidney disease (1)
1	-	-	Polycystic kidney disease (1)
1	-	-	Polycystic kidney disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

Splicing

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

Other links and lift over

dbSNP: rs1057518797; hg19: chr4-88929242;