4-88023359-C-T

Variant names:

• chr4-88023359-C-T
• rs2725227
• NM_000297.4:c.709+3788C>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.709+3788C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,912 control chromosomes in the GnomAD database, including 18,762 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 0.49 (18762 hom., cov: 31)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 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.709+3788C>T		intron	N/A	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.709+3788C>T		intron	N/A	NP_001427473.1
	PKD2	NR_156488.2		n.808+3788C>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.709+3788C>T		intron	N/A	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.709+3788C>T		intron	N/A	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.709+3788C>T		intron	N/A	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74170 AN: 151794 Hom.: 18752 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.489 AC: 74228 AN: 151912 Hom.: 18762 Cov.: 31 AF XY: 0.494 AC XY: 36705 AN XY: 74250

African (AFR) AF: 0.574 AC: 23782 AN: 41444

American (AMR) AF: 0.514 AC: 7841 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3470

East Asian (EAS) AF: 0.712 AC: 3658 AN: 5140

South Asian (SAS) AF: 0.597 AC: 2865 AN: 4800

European-Finnish (FIN) AF: 0.452 AC: 4763 AN: 10536

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28409 AN: 67942

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.439 Hom.: 20609

Bravo AF: 0.500

Asia WGS AF: 0.654 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.76
PhyloP100		-0.69
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: rs2725227; hg19: chr4-88944511;