4-88007720-C-G

Variant names:

• chr4-88007720-C-G
• rs552115097
• NM_000297.4:c.-14C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000297.4(PKD2):​c.-14C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKD2 NM_000297.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• 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

ENSG00000286618 (HGNC:):

ENSG00000289034 (HGNC:58844):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

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.-14C>G		5_prime_UTR	Exon 1 of 15	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.-14C>G		5_prime_UTR	Exon 1 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.86C>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.-14C>G		5_prime_UTR	Exon 1 of 15	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.-14C>G		5_prime_UTR	Exon 1 of 15	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.-14C>G		5_prime_UTR	Exon 1 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1043206 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 506540

African (AFR) AF: 0.00 AC: 0 AN: 20108

American (AMR) AF: 0.00 AC: 0 AN: 12304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13502

East Asian (EAS) AF: 0.00 AC: 0 AN: 14870

South Asian (SAS) AF: 0.00 AC: 0 AN: 39038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3024

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 885922

Other (OTH) AF: 0.00 AC: 0 AN: 38206

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.28
PromoterAI		0.081	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

dbSNP: rs552115097; hg19: chr4-88928872;