rs62310565

Variant names:

• chr4-88019442-C-T
• rs62310565
• NM_000297.4:c.596-16C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-88019442-C-T
• chr4-88019442-C-A

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.596-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,219,848 control chromosomes in the GnomAD database, including 448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (38 hom., cov: 32)
  • Exomes 𝑓: 0.024 (410 hom.)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.918
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 4-88019442-C-T is Benign according to our data. Variant chr4-88019442-C-T is described in ClinVar as Benign. ClinVar VariationId is 255796.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 = 0.0195 (2963/151796) while in subpopulation SAS AF = 0.0307 (147/4786). AF 95% confidence interval is 0.0267. There are 38 homozygotes in GnomAd4. There are 1480 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 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.596-16C>T		intron	N/A	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.596-16C>T		intron	N/A	NP_001427473.1
	PKD2	NR_156488.2		n.695-16C>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.596-16C>T		intron	N/A	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.596-16C>T		intron	N/A	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.596-16C>T		intron	N/A	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2963 AN: 151682 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.00436

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0305

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0149

GnomAD2 exomes AF: 0.0228 AC: 5548 AN: 243680 AF XY: 0.0234

Gnomad AFR exome AF: 0.00295

Gnomad AMR exome AF: 0.0320

Gnomad ASJ exome AF: 0.00689

Gnomad EAS exome AF: 0.000392

Gnomad FIN exome AF: 0.0314

Gnomad NFE exome AF: 0.0254

Gnomad OTH exome AF: 0.0182

GnomAD4 exome AF: 0.0242 AC: 25805 AN: 1068052 Hom.: 410 Cov.: 15 AF XY: 0.0244 AC XY: 13396 AN XY: 549788

African (AFR) AF: 0.00380 AC: 97 AN: 25494

American (AMR) AF: 0.0308 AC: 1353 AN: 43980

Ashkenazi Jewish (ASJ) AF: 0.00773 AC: 183 AN: 23676

East Asian (EAS) AF: 0.000293 AC: 11 AN: 37494

South Asian (SAS) AF: 0.0289 AC: 2231 AN: 77316

European-Finnish (FIN) AF: 0.0301 AC: 1594 AN: 53020

Middle Eastern (MID) AF: 0.0149 AC: 74 AN: 4952

European-Non Finnish (NFE) AF: 0.0256 AC: 19310 AN: 754764

Other (OTH) AF: 0.0201 AC: 952 AN: 47356

GnomAD4 genome AF: 0.0195 AC: 2963 AN: 151796 Hom.: 38 Cov.: 32 AF XY: 0.0200 AC XY: 1480 AN XY: 74160

African (AFR) AF: 0.00435 AC: 180 AN: 41398

American (AMR) AF: 0.0242 AC: 370 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5156

South Asian (SAS) AF: 0.0307 AC: 147 AN: 4786

European-Finnish (FIN) AF: 0.0332 AC: 347 AN: 10462

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0270 AC: 1837 AN: 67952

Other (OTH) AF: 0.0147 AC: 31 AN: 2106

Alfa AF: 0.0237 Hom.: 9

Bravo AF: 0.0178

Asia WGS AF: 0.0140 AC: 49 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.1
DANN	Benign	0.59
PhyloP100		-0.92
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: rs62310565; hg19: chr4-88940594;