4-88007751-C-G

Variant names:

• chr4-88007751-C-G
• NM_000297.4:c.18C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_000297.4(PKD2):​c.18C>G​(p.Arg6Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 1,052,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: PKD2 NM_000297.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.708
• Publications: 0 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:):

ENSG00000289034 (HGNC:58844):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 4-88007751-C-G is Benign according to our data. Variant chr4-88007751-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2413831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.708 with no splicing effect.

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.18C>G	p.Arg6Arg	synonymous	Exon 1 of 15	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.18C>G	p.Arg6Arg	synonymous	Exon 1 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.117C>G		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.18C>G	p.Arg6Arg	synonymous	Exon 1 of 15	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.18C>G	p.Arg6Arg	synonymous	Exon 1 of 15	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.18C>G	p.Arg6Arg	synonymous	Exon 1 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000665 AC: 7 AN: 1052678 Hom.: 0 Cov.: 28 AF XY: 0.00000781 AC XY: 4 AN XY: 511878

African (AFR) AF: 0.00 AC: 0 AN: 20500

American (AMR) AF: 0.0000659 AC: 1 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14188

East Asian (EAS) AF: 0.00 AC: 0 AN: 14310

South Asian (SAS) AF: 0.00 AC: 0 AN: 40750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2838

European-Non Finnish (NFE) AF: 0.00000674 AC: 6 AN: 889990

Other (OTH) AF: 0.00 AC: 0 AN: 38674

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant polycystic kidney disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		-0.71
PromoterAI		0.10	Neutral

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

hg19: chr4-88928903;