rs750077647

chr4-88008021-CGAGGAG-Cchr4-88008021-CGAGGAG-CGAGchr4-88008021-CGAGGAG-CGAGGAGGAGchr4-88008021-CGAGGAG-CGAGGAGGAGGAGchr4-88008021-CGAGGAG-CGAGGAGGAGGAGGAG

Variant summary

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

The NM_000297.4(PKD2):c.302_307del(p.Glu101_Glu102del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000178 in 1,516,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: PKD2 NM_000297.4 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2	NM_000297.4	c.302_307del	p.Glu101_Glu102del	inframe_deletion	1/15	ENST00000237596.7
PKD2	XM_011532028.3	c.302_307del	p.Glu101_Glu102del	inframe_deletion	1/14
PKD2	NR_156488.2	n.401_406del		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2	ENST00000237596.7	c.302_307del	p.Glu101_Glu102del	inframe_deletion	1/15	1	NM_000297.4	P1
	ENST00000662475.1	n.112+339_112+344del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150528 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.000483

GnomAD4 exome AF: 0.0000190 AC: 26 AN: 1365532 Hom.: 0 AF XY: 0.0000193 AC XY: 13 AN XY: 673648

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000872

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.0000297

Gnomad4 NFE exome AF: 0.0000196

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150528 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73458

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000483

Alfa AF: 0.000305 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2021

In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; In-frame deletion of 2 amino acids with an unclear effect on protein function -

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: rs750077647; hg19: chr4-88929173;