chr4-88007652-G-C

Variant names:

• chr4-88007652-G-C
• rs529779778
• NM_000297.4:c.-82G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000297.4(PKD2):​c.-82G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 941,466 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (33 hom., cov: 33)
  • Exomes 𝑓: 0.022 (234 hom.)
• Consequence: PKD2 NM_000297.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.389
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 4-88007652-G-C is Benign according to our data. Variant chr4-88007652-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 350007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0168 (2538/150916) while in subpopulation SAS AF = 0.047 (227/4832). AF 95% confidence interval is 0.042. There are 33 homozygotes in GnomAd4. There are 1373 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AD,AR gene

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.-82G>C		5_prime_UTR	Exon 1 of 15	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.-82G>C		5_prime_UTR	Exon 1 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.18G>C		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.-82G>C		5_prime_UTR	Exon 1 of 15	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.-82G>C		5_prime_UTR	Exon 1 of 15	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.-82G>C		5_prime_UTR	Exon 1 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2534 AN: 150806 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.00397

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0373

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0174

GnomAD4 exome AF: 0.0220 AC: 17375 AN: 790550 Hom.: 234 Cov.: 11 AF XY: 0.0221 AC XY: 8260 AN XY: 374034

African (AFR) AF: 0.00214 AC: 32 AN: 14920

American (AMR) AF: 0.0120 AC: 32 AN: 2670

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 203 AN: 6196

East Asian (EAS) AF: 0.000125 AC: 1 AN: 7978

South Asian (SAS) AF: 0.0467 AC: 820 AN: 17548

European-Finnish (FIN) AF: 0.0297 AC: 209 AN: 7046

Middle Eastern (MID) AF: 0.0220 AC: 49 AN: 2230

European-Non Finnish (NFE) AF: 0.0218 AC: 15390 AN: 704500

Other (OTH) AF: 0.0233 AC: 639 AN: 27462

GnomAD4 genome AF: 0.0168 AC: 2538 AN: 150916 Hom.: 33 Cov.: 33 AF XY: 0.0186 AC XY: 1373 AN XY: 73766

African (AFR) AF: 0.00406 AC: 168 AN: 41412

American (AMR) AF: 0.0142 AC: 215 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.0373 AC: 129 AN: 3456

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.0470 AC: 227 AN: 4832

European-Finnish (FIN) AF: 0.0412 AC: 416 AN: 10100

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.0196 AC: 1323 AN: 67520

Other (OTH) AF: 0.0172 AC: 36 AN: 2096

Alfa AF: 0.00397 Hom.: 2

Bravo AF: 0.0139

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant polycystic kidney disease (1)
-	-	1	Polycystic kidney disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.39
PromoterAI		0.55	Over-expression

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs529779778; hg19: chr4-88928804;