4-88008021-CGAGGAG-CGAG
Variant names:
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_000297.4(PKD2):c.305_307delAGG(p.Glu102del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00728 in 1,219,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0073 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PKD2
NM_000297.4 disruptive_inframe_deletion
NM_000297.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.02
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 was made for transcript
Our verdict: Benign. The variant received -10 ACMG points.
BP6
Variant 4-88008021-CGAG-C is Benign according to our data. Variant chr4-88008021-CGAG-C is described in ClinVar as [Benign]. Clinvar id is 219942.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-88008021-CGAG-C is described in Lovd as [Likely_benign]. Variant chr4-88008021-CGAG-C is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00728 (8882/1219582) while in subpopulation SAS AF = 0.0157 (928/59114). AF 95% confidence interval is 0.0149. There are 0 homozygotes in GnomAdExome4. There are 4460 alleles in the male GnomAdExome4 subpopulation. This position FAILED quality control check.
BS2
High AC in GnomAdExome4 at 8882 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKD2 | NM_000297.4 | c.305_307delAGG | p.Glu102del | disruptive_inframe_deletion | Exon 1 of 15 | ENST00000237596.7 | NP_000288.1 | |
PKD2 | XM_011532028.3 | c.305_307delAGG | p.Glu102del | disruptive_inframe_deletion | Exon 1 of 14 | XP_011530330.1 | ||
PKD2 | NR_156488.2 | n.404_406delAGG | non_coding_transcript_exon_variant | Exon 1 of 14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PKD2 | ENST00000237596.7 | c.305_307delAGG | p.Glu102del | disruptive_inframe_deletion | Exon 1 of 15 | 1 | NM_000297.4 | ENSP00000237596.2 | ||
ENSG00000286618 | ENST00000662475.1 | n.112+342_112+344delCTC | intron_variant | Intron 1 of 2 | ||||||
PKD2 | ENST00000506727.1 | n.-210_-208delGAG | upstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000200 AC: 30AN: 150308Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
30
AN:
150308
Hom.:
Cov.:
32
Gnomad AFR
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GnomAD2 exomes AF: 0.0244 AC: 2381AN: 97700 AF XY: 0.0232 show subpopulations
GnomAD2 exomes
AF:
AC:
2381
AN:
97700
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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GnomAD4 exome AF: 0.00728 AC: 8882AN: 1219582Hom.: 0 AF XY: 0.00751 AC XY: 4460AN XY: 594154 show subpopulations
GnomAD4 exome
AF:
AC:
8882
AN:
1219582
Hom.:
AF XY:
AC XY:
4460
AN XY:
594154
Gnomad4 AFR exome
AF:
AC:
281
AN:
27494
Gnomad4 AMR exome
AF:
AC:
431
AN:
28986
Gnomad4 ASJ exome
AF:
AC:
217
AN:
21238
Gnomad4 EAS exome
AF:
AC:
467
AN:
29868
Gnomad4 SAS exome
AF:
AC:
928
AN:
59114
Gnomad4 FIN exome
AF:
AC:
264
AN:
27528
Gnomad4 NFE exome
AF:
AC:
5820
AN:
970022
Gnomad4 Remaining exome
AF:
AC:
445
AN:
50226
⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Heterozygous variant carriers
0
1249
2498
3746
4995
6244
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
118
236
354
472
590
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000199 AC: 30AN: 150398Hom.: 0 Cov.: 32 AF XY: 0.000218 AC XY: 16AN XY: 73428 show subpopulations
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
30
AN:
150398
Hom.:
Cov.:
32
AF XY:
AC XY:
16
AN XY:
73428
Gnomad4 AFR
AF:
AC:
0.0000241768
AN:
0.0000241768
Gnomad4 AMR
AF:
AC:
0.0003306
AN:
0.0003306
Gnomad4 ASJ
AF:
AC:
0
AN:
0
Gnomad4 EAS
AF:
AC:
0
AN:
0
Gnomad4 SAS
AF:
AC:
0
AN:
0
Gnomad4 FIN
AF:
AC:
0.000606183
AN:
0.000606183
Gnomad4 NFE
AF:
AC:
0.000252473
AN:
0.000252473
Gnomad4 OTH
AF:
AC:
0.000479846
AN:
0.000479846
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:2
-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
Autosomal dominant polycystic kidney disease Benign:1
Nov 30, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Mutation Taster
=67/33
polymorphism
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at