rs398122397
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001257180.2(SLC20A2):c.583_584del(p.Val195LeufsTer62) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SLC20A2
NM_001257180.2 frameshift
NM_001257180.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.13
Genes affected
SLC20A2 (HGNC:10947): (solute carrier family 20 member 2) This gene encodes a member of the inorganic phosphate transporter family. The encoded protein is a type 3 sodium-dependent phosphate symporter that plays an important role in phosphate homeostasis by mediating cellular phosphate uptake. The encoded protein also confers susceptibility to viral infection as a gamma-retroviral receptor. Mutations in this gene may play a role in familial idiopathic basal ganglia calcification. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 8-42459924-GAC-G is Pathogenic according to our data. Variant chr8-42459924-GAC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 75233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC20A2 | NM_001257180.2 | c.583_584del | p.Val195LeufsTer62 | frameshift_variant | 5/11 | ENST00000520262.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC20A2 | ENST00000520262.6 | c.583_584del | p.Val195LeufsTer62 | frameshift_variant | 5/11 | 2 | NM_001257180.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2018 | This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual and a family affected with idiopathic basal ganglia calcification (PMID: 23334463, Invitae). Loss-of-function variants in SLC20A2 are known to be pathogenic (PMID: 23334463). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Val195Leufs*62) in the SLC20A2 gene. It is expected to result in an absent or disrupted protein product. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2022 | Identified in a family with basal ganglia calcifications, however, it is unknown whether the family was screened for variants in other genes associated with idiopathic basal ganglia calcification (Hsu et al., 2013); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26147798, 23334463) - |
Idiopathic basal ganglia calcification 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2013 | - - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at