rs2728111

Variant names:

• chr4-88030984-C-T
• rs2728111
• NM_000297.4:c.710-5236C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000297.4(PKD2):​c.710-5236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,254 control chromosomes in the GnomAD database, including 49,967 homozygotes. 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: 𝑓 0.81 (49967 hom., cov: 33)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

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.710-5236C>T		intron	N/A	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.710-5236C>T		intron	N/A	NP_001427473.1
	PKD2	NR_156488.2		n.809-5236C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.710-5236C>T		intron	N/A	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.710-5236C>T		intron	N/A	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.710-5236C>T		intron	N/A	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122777 AN: 152136 Hom.: 49919 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.807 AC: 122881 AN: 152254 Hom.: 49967 Cov.: 33 AF XY: 0.810 AC XY: 60331 AN XY: 74450

African (AFR) AF: 0.909 AC: 37771 AN: 41564

American (AMR) AF: 0.772 AC: 11810 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2462 AN: 3468

East Asian (EAS) AF: 0.714 AC: 3694 AN: 5172

South Asian (SAS) AF: 0.810 AC: 3908 AN: 4826

European-Finnish (FIN) AF: 0.833 AC: 8833 AN: 10600

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51840 AN: 68012

Other (OTH) AF: 0.766 AC: 1620 AN: 2116

Alfa AF: 0.786 Hom.: 18050

Bravo AF: 0.807

Asia WGS AF: 0.778 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.72
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2728111; hg19: chr4-88952136;