4-88075950-C-T

Variant names:

• chr4-88075950-C-T
• rs2728121
• NM_000297.4:c.*256C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000297.4(PKD2):​c.*256C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 460,598 control chromosomes in the GnomAD database, including 6,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1749 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4362 hom.)
• Consequence: PKD2 NM_000297.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0690
• Publications: 23 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=-0.89).
• BP6: Variant 4-88075950-C-T is Benign according to our data. Variant chr4-88075950-C-T is described in ClinVar as Benign. ClinVar VariationId is 350037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 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.*256C>T		3_prime_UTR	Exon 15 of 15	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.*256C>T		3_prime_UTR	Exon 14 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.3141C>T		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.*256C>T		3_prime_UTR	Exon 15 of 15	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.*256C>T		3_prime_UTR	Exon 15 of 15	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.*256C>T		3_prime_UTR	Exon 14 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20504 AN: 151886 Hom.: 1746 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.150 AC: 46170 AN: 308594 Hom.: 4362 Cov.: 0 AF XY: 0.150 AC XY: 24731 AN XY: 164514

African (AFR) AF: 0.133 AC: 1232 AN: 9234

American (AMR) AF: 0.221 AC: 2975 AN: 13476

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 1251 AN: 9446

East Asian (EAS) AF: 0.438 AC: 8603 AN: 19646

South Asian (SAS) AF: 0.152 AC: 5719 AN: 37666

European-Finnish (FIN) AF: 0.139 AC: 2093 AN: 15094

Middle Eastern (MID) AF: 0.113 AC: 144 AN: 1278

European-Non Finnish (NFE) AF: 0.116 AC: 21431 AN: 185074

Other (OTH) AF: 0.154 AC: 2722 AN: 17680

GnomAD4 genome AF: 0.135 AC: 20547 AN: 152004 Hom.: 1749 Cov.: 32 AF XY: 0.139 AC XY: 10354 AN XY: 74282

African (AFR) AF: 0.127 AC: 5267 AN: 41460

American (AMR) AF: 0.165 AC: 2512 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3466

East Asian (EAS) AF: 0.464 AC: 2396 AN: 5160

South Asian (SAS) AF: 0.142 AC: 687 AN: 4824

European-Finnish (FIN) AF: 0.130 AC: 1365 AN: 10538

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7479 AN: 67986

Other (OTH) AF: 0.124 AC: 262 AN: 2108

Alfa AF: 0.120 Hom.: 4157

Bravo AF: 0.141

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.89
CADD	Benign	3.5
DANN	Benign	0.52
PhyloP100		0.069
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: rs2728121; hg19: chr4-88997102;