4-88008021-CGAGGAG-CGAG

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 4.02
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 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
PKD2NM_000297.4 linkc.305_307delAGG p.Glu102del disruptive_inframe_deletion Exon 1 of 15 ENST00000237596.7 NP_000288.1 Q13563-1Q9UEU6
PKD2XM_011532028.3 linkc.305_307delAGG p.Glu102del disruptive_inframe_deletion Exon 1 of 14 XP_011530330.1
PKD2NR_156488.2 linkn.404_406delAGG non_coding_transcript_exon_variant Exon 1 of 14

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKD2ENST00000237596.7 linkc.305_307delAGG p.Glu102del disruptive_inframe_deletion Exon 1 of 15 1 NM_000297.4 ENSP00000237596.2 Q13563-1
ENSG00000286618ENST00000662475.1 linkn.112+342_112+344delCTC intron_variant Intron 1 of 2
PKD2ENST00000506727.1 linkn.-210_-208delGAG upstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000200
AC:
30
AN:
150308
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000331
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000606
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000252
Gnomad OTH
AF:
0.000484
GnomAD2 exomes
AF:
0.0244
AC:
2381
AN:
97700
AF XY:
0.0232
show subpopulations
Gnomad AFR exome
AF:
0.0575
Gnomad AMR exome
AF:
0.0171
Gnomad ASJ exome
AF:
0.00999
Gnomad EAS exome
AF:
0.0583
Gnomad FIN exome
AF:
0.00609
Gnomad NFE exome
AF:
0.0277
Gnomad OTH exome
AF:
0.0330
GnomAD4 exome
AF:
0.00728
AC:
8882
AN:
1219582
Hom.:
0
AF XY:
0.00751
AC XY:
4460
AN XY:
594154
show subpopulations
Gnomad4 AFR exome
AF:
0.0102
AC:
281
AN:
27494
Gnomad4 AMR exome
AF:
0.0149
AC:
431
AN:
28986
Gnomad4 ASJ exome
AF:
0.0102
AC:
217
AN:
21238
Gnomad4 EAS exome
AF:
0.0156
AC:
467
AN:
29868
Gnomad4 SAS exome
AF:
0.0157
AC:
928
AN:
59114
Gnomad4 FIN exome
AF:
0.00959
AC:
264
AN:
27528
Gnomad4 NFE exome
AF:
0.00600
AC:
5820
AN:
970022
Gnomad4 Remaining exome
AF:
0.00886
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:
30
AN:
150398
Hom.:
0
Cov.:
32
AF XY:
0.000218
AC XY:
16
AN XY:
73428
show subpopulations
Gnomad4 AFR
AF:
0.0000242
AC:
0.0000241768
AN:
0.0000241768
Gnomad4 AMR
AF:
0.000331
AC:
0.0003306
AN:
0.0003306
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.000606
AC:
0.000606183
AN:
0.000606183
Gnomad4 NFE
AF:
0.000252
AC:
0.000252473
AN:
0.000252473
Gnomad4 OTH
AF:
0.000480
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:
0.0325
Hom.:
1

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
Mutation Taster
=67/33
polymorphism

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: rs750077647; hg19: chr4-88929173; COSMIC: COSV52938297; COSMIC: COSV52938297; API