4-88008021-CGAGGAGGAG-CGAG

Variant names:

• chr4-88008021-CGAGGAG-C
• rs750077647
• NM_000297.4:c.302_307delAGGAGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_000297.4(PKD2):​c.302_307delAGGAGG​(p.Glu101_Glu102del) variant causes a disruptive 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 (★). Synonymous variant affecting the same amino acid position (i.e. E101E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: PKD2 NM_000297.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02
• Publications: 3 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: ClinGen, Orphanet
• polycystic kidney disease 2

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

ENSG00000286618 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000297.4

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	NM_000297.4	MANE Select	c.302_307delAGGAGG	p.Glu101_Glu102del	disruptive_inframe_deletion	Exon 1 of 15	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.302_307delAGGAGG	p.Glu101_Glu102del	disruptive_inframe_deletion	Exon 1 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.401_406delAGGAGG		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.302_307delAGGAGG	p.Glu101_Glu102del	disruptive_inframe_deletion	Exon 1 of 15	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.302_307delAGGAGG	p.Glu101_Glu102del	disruptive_inframe_deletion	Exon 1 of 15	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.302_307delAGGAGG	p.Glu101_Glu102del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000597507.1

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

GnomAD2 exomes AF: 0.0000716 AC: 7 AN: 97700 AF XY: 0.0000749

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00

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

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

African (AFR) AF: 0.00 AC: 0 AN: 30136

American (AMR) AF: 0.00 AC: 0 AN: 33882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24684

East Asian (EAS) AF: 0.0000872 AC: 3 AN: 34416

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 77134

European-Finnish (FIN) AF: 0.0000297 AC: 1 AN: 33696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5606

European-Non Finnish (NFE) AF: 0.0000196 AC: 21 AN: 1068862

Other (OTH) AF: 0.00 AC: 0 AN: 57116

⚠️ 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.

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

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

African (AFR) AF: 0.00 AC: 0 AN: 41268

American (AMR) AF: 0.00 AC: 0 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67408

Other (OTH) AF: 0.000483 AC: 1 AN: 2070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000305 Hom.: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=149/51	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs750077647; hg19: chr4-88929173;