chr4-88037340-G-A

Variant names:

• chr4-88037340-G-A
• rs2725222
• NM_000297.4:c.844-911G>A

Variant summary

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

The NM_000297.4(PKD2):​c.844-911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,048 control chromosomes in the GnomAD database, including 14,213 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 0.43 (14213 hom., cov: 32)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 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.844-911G>A		intron	N/A	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.844-911G>A		intron	N/A	NP_001427473.1
	PKD2	NR_156488.2		n.943-911G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.844-911G>A		intron	N/A	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.844-911G>A		intron	N/A	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.844-911G>A		intron	N/A	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65541 AN: 151928 Hom.: 14188 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.432 AC: 65634 AN: 152048 Hom.: 14213 Cov.: 32 AF XY: 0.428 AC XY: 31823 AN XY: 74320

African (AFR) AF: 0.452 AC: 18758 AN: 41460

American (AMR) AF: 0.436 AC: 6673 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1333 AN: 3464

East Asian (EAS) AF: 0.259 AC: 1341 AN: 5174

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4818

European-Finnish (FIN) AF: 0.432 AC: 4553 AN: 10542

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30352 AN: 67986

Other (OTH) AF: 0.411 AC: 869 AN: 2114

Alfa AF: 0.432 Hom.: 30150

Bravo AF: 0.431

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-1.1
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: rs2725222; hg19: chr4-88958492;