4-88075950-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0690
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PKD2NM_000297.4 linkc.*256C>T 3_prime_UTR_variant 15/15 ENST00000237596.7 NP_000288.1 Q13563-1Q9UEU6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PKD2ENST00000237596.7 linkc.*256C>T 3_prime_UTR_variant 15/151 NM_000297.4 ENSP00000237596.2 Q13563-1

Frequencies

GnomAD3 genomes
AF:
0.135
AC:
20504
AN:
151886
Hom.:
1746
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.133
Gnomad4 AMR exome
AF:
0.221
Gnomad4 ASJ exome
AF:
0.132
Gnomad4 EAS exome
AF:
0.438
Gnomad4 SAS exome
AF:
0.152
Gnomad4 FIN exome
AF:
0.139
Gnomad4 NFE exome
AF:
0.116
Gnomad4 OTH exome
AF:
0.154
GnomAD4 genome
AF:
0.135
AC:
20547
AN:
152004
Hom.:
1749
Cov.:
32
AF XY:
0.139
AC XY:
10354
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.127
Gnomad4 AMR
AF:
0.165
Gnomad4 ASJ
AF:
0.136
Gnomad4 EAS
AF:
0.464
Gnomad4 SAS
AF:
0.142
Gnomad4 FIN
AF:
0.130
Gnomad4 NFE
AF:
0.110
Gnomad4 OTH
AF:
0.124
Alfa
AF:
0.114
Hom.:
1382
Bravo
AF:
0.141
Asia WGS
AF:
0.327
AC:
1136
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Polycystic kidney disease 2 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
3.5
DANN
Benign
0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2728121; hg19: chr4-88997102; API