rs1555448280

Positions:

• chr16-2097386-CAGCCCATGGCCCGCCTGG-CGGCCAT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001009944.3(PKD1):​c.10320_10337delCCAGGCGGGCCATGGGCTinsATGGCC​(p.Gln3441_Leu3446delinsTrpPro) variant causes a missense, disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKD1 NM_001009944.3 missense, disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001009944.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1	NM_001009944.3	c.10320_10337delCCAGGCGGGCCATGGGCTinsATGGCC	p.Gln3441_Leu3446delinsTrpPro	missense_variant, disruptive_inframe_deletion		ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9	c.10320_10337delCCAGGCGGGCCATGGGCTinsATGGCC	p.Gln3441_Leu3446delinsTrpPro	missense_variant, disruptive_inframe_deletion		1	NM_001009944.3	ENSP00000262304.4
PKD1	ENST00000423118.5	c.10317_10334delCCAGGCGGGCCATGGGCTinsATGGCC	p.Gln3440_Leu3445delinsTrpPro	missense_variant, disruptive_inframe_deletion		1		ENSP00000399501.1
PKD1	ENST00000487932.5	n.*1513_*1530delCCAGGCGGGCCATGGGCTinsATGGCC		non_coding_transcript_exon_variant	20/30	5		ENSP00000457132.1
PKD1	ENST00000487932.5	n.*1513_*1530delCCAGGCGGGCCATGGGCTinsATGGCC		3_prime_UTR_variant	20/30	5		ENSP00000457132.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 30, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555448280; hg19: chr16-2147388;