chr4-88008153-G-A
Position:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000297.4(PKD2):c.420G>A(p.Gly140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,462,896 control chromosomes in the GnomAD database, including 9,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.089 ( 929 hom., cov: 32)
Exomes 𝑓: 0.10 ( 8372 hom. )
Consequence
PKD2
NM_000297.4 synonymous
NM_000297.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: -1.02
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 4-88008153-G-A is Benign according to our data. Variant chr4-88008153-G-A is described in ClinVar as [Benign]. Clinvar id is 92795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-88008153-G-A is described in Lovd as [Benign]. Variant chr4-88008153-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.02 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2 | NM_000297.4 | c.420G>A | p.Gly140= | synonymous_variant | 1/15 | ENST00000237596.7 | |
PKD2 | XM_011532028.3 | c.420G>A | p.Gly140= | synonymous_variant | 1/14 | ||
PKD2 | NR_156488.2 | n.519G>A | non_coding_transcript_exon_variant | 1/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2 | ENST00000237596.7 | c.420G>A | p.Gly140= | synonymous_variant | 1/15 | 1 | NM_000297.4 | P1 | |
ENST00000662475.1 | n.112+213C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0889 AC: 13486AN: 151746Hom.: 924 Cov.: 32
GnomAD3 genomes
AF:
AC:
13486
AN:
151746
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.133 AC: 11224AN: 84630Hom.: 1049 AF XY: 0.118 AC XY: 5664AN XY: 48146
GnomAD3 exomes
AF:
AC:
11224
AN:
84630
Hom.:
AF XY:
AC XY:
5664
AN XY:
48146
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.104 AC: 135815AN: 1311042Hom.: 8372 Cov.: 36 AF XY: 0.102 AC XY: 65698AN XY: 646084
GnomAD4 exome
AF:
AC:
135815
AN:
1311042
Hom.:
Cov.:
36
AF XY:
AC XY:
65698
AN XY:
646084
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0890 AC: 13515AN: 151854Hom.: 929 Cov.: 32 AF XY: 0.0906 AC XY: 6721AN XY: 74224
GnomAD4 genome
AF:
AC:
13515
AN:
151854
Hom.:
Cov.:
32
AF XY:
AC XY:
6721
AN XY:
74224
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
525
AN:
3456
ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal dominant polycystic kidney disease Benign:2
Benign, criteria provided, single submitter | research | Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research | Jan 01, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Polycystic kidney disease 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This 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. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 02, 2020 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 06, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 25, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 07, 2016 | - - |
Polycystic kidney disease Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The PKD2 p.Gly140Gly variant was identified as a polymorphism in 7 of 172 proband chromosomes (frequency: 0.041) from individuals or families with Autosomal Dominant Polycystic Kidney Disease and (Bataille 2011, Liu 2015). The variant was also identified in dbSNP (ID: rs2728118 “With Benign allele”, with a minor allele frequency of 0.1144 (573 of 5000 chromosomes in the 1000 Genomes Project). This variant was identified in the Exome Aggregation Consortium database (March 14, 2016) in 662 (27 homozygous) of 10588 chromosomes (freq. 0.06 ) in the following populations: East Asian in 32 of 130 chromosomes (freq. 0.25), Latino in 12 of 96 chromosomes (freq. 0.125), other in 10 of 120 chromosomes (freq. 0.08), European (Non-Finnish) in 194 of 2688 chromosomes (freq. 0.07), South Asian in 409 of 7348 chromosomes (freq. 0.06), and African in 5 of 206 chromosomes (freq. 0.02), but was not seen in the Finnish population, increasing the likelihood this could be a low frequency benign variant. In the ClinVar database the variant was identified as benign by Emory Genetics laboratory and in Clinvitae it was identified as benign by EmyClass. In the Mayo Clinic PKD database the variant was identified as likely neutral. In LOVD-PKD2 database the variant was identified 6X and as having no effect. In mRNA transcript analysis in the parents of one patient, the p.Gly140Gly variant occurred in trans to a variant (c.595_595+ 14del) that is predicted to affect splicing and is subjected to nonsense mediated decay (Liu 2015). The p.Gly140Gly variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign. - |
PKD2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 05, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
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