rs144968710
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000297.4(PKD2):c.1830G>A(p.Ala610=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000591 in 1,613,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 1 hom. )
Consequence
PKD2
NM_000297.4 synonymous
NM_000297.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.17
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 4-88056199-G-A is Benign according to our data. Variant chr4-88056199-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-88056199-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-2.17 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000906 (138/152254) while in subpopulation AFR AF= 0.00152 (63/41538). AF 95% confidence interval is 0.00122. There are 0 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 138 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2 | NM_000297.4 | c.1830G>A | p.Ala610= | synonymous_variant | 8/15 | ENST00000237596.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2 | ENST00000237596.7 | c.1830G>A | p.Ala610= | synonymous_variant | 8/15 | 1 | NM_000297.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000907 AC: 138AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000868 AC: 218AN: 251104Hom.: 0 AF XY: 0.000884 AC XY: 120AN XY: 135694
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GnomAD4 exome AF: 0.000558 AC: 816AN: 1461202Hom.: 1 Cov.: 30 AF XY: 0.000592 AC XY: 430AN XY: 726962
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GnomAD4 genome AF: 0.000906 AC: 138AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000658 AC XY: 49AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 21, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | PKD2: BP4, BP7, BS1 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2021 | This variant is associated with the following publications: (PMID: 24658975) - |
Polycystic kidney disease 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 27, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Polycystic kidney disease Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The PKD2 p.Ala610Ala variant was identified in dbSNP (ID: rs144968710) as “N/A”, ADPKD Mutation Database (likely neutral), 1000 Genomes Project in 8 of 5000 chromosomes (frequency: 0.002), NHLBI GO Exome Sequencing Project in 8 of 8600 European American and in 10 of 4406 African American alleles, the Exome Aggregation Consortium database (August 8, 2016) in 94 of 121226 chromosomes (freq. 0.0008) in the following populations: European in 39 of 66662 chromosomes (freq. 0.0006), African in 19 of 10406 chromosomes (freq. 0.002), South Asian in 19 of 16482 chromosomes (freq. 0.001), Latino in 12 of 11560 chromosomes (freq. 0.001), Finish in 3 of 6600 chromosomes (freq. 0.0005), Other 2 in 906 chromosomes (freq. 0.002), increasing the likelihood this could be a low frequency benign variant. The p.Ala610Ala 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. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Autosomal dominant polycystic kidney disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at