chr4-88038770-G-C

Variant names:

• chr4-88038770-G-C
• rs2725220
• NM_000297.4:c.1094+269G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000297.4(PKD2):​c.1094+269G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,976 control chromosomes in the GnomAD database, including 23,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (23788 hom., cov: 32)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.321
• Publications: 26 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-88038770-G-C is Benign according to our data. Variant chr4-88038770-G-C is described in ClinVar as Benign. ClinVar VariationId is 1234483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 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.1094+269G>C		intron	N/A	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.1094+269G>C		intron	N/A	NP_001427473.1
	PKD2	NR_156488.2		n.1193+269G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.1094+269G>C		intron	N/A	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.1094+269G>C		intron	N/A	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.1094+269G>C		intron	N/A	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82314 AN: 151858 Hom.: 23729 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.542 AC: 82440 AN: 151976 Hom.: 23788 Cov.: 32 AF XY: 0.536 AC XY: 39802 AN XY: 74276

African (AFR) AF: 0.756 AC: 31349 AN: 41460

American (AMR) AF: 0.443 AC: 6767 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3464

East Asian (EAS) AF: 0.253 AC: 1307 AN: 5174

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4816

European-Finnish (FIN) AF: 0.453 AC: 4772 AN: 10536

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32902 AN: 67950

Other (OTH) AF: 0.501 AC: 1056 AN: 2106

Alfa AF: 0.460 Hom.: 8316

Bravo AF: 0.551

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.35
PhyloP100		-0.32
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: rs2725220; hg19: chr4-88959922;