rs886041393
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001257180.2(SLC20A2):c.509del(p.Leu170Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
SLC20A2
NM_001257180.2 frameshift
NM_001257180.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.32
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 8-42463011-TA-T is Pathogenic according to our data. Variant chr8-42463011-TA-T is described in ClinVar as [Pathogenic]. Clinvar id is 280118.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.509del | p.Leu170Ter | frameshift_variant | 4/11 | ENST00000520262.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC20A2 | ENST00000520262.6 | c.509del | p.Leu170Ter | frameshift_variant | 4/11 | 2 | NM_001257180.2 | P1 | |
SLC20A2 | ENST00000342228.7 | c.509del | p.Leu170Ter | frameshift_variant | 4/11 | 1 | P1 | ||
SLC20A2 | ENST00000520179.5 | c.509del | p.Leu170Ter | frameshift_variant | 4/11 | 1 | P1 | ||
SLC20A2 | ENST00000518660.5 | n.235del | non_coding_transcript_exon_variant | 2/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SLC20A2-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2023 | The SLC20A2 c.509delT variant is predicted to result in an in-frame deletion (p.Leu170fs). This variant was reported in a family with basal ganglia calcification. However, out of 11 affected family members, two members did not carry this variant (Family F1 in Hsu et al. 2013. PubMed ID: 23334463). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in SLC20A2 are expected to be pathogenic. This variant is interpreted as pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 23, 2015 | The L170X variant in the SLC20A2 gene has been reported previously in a family affected with idiopathic basal ganglia calcification (Hsu et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The L170X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret L170X as a pathogenic variant. - |
Idiopathic basal ganglia calcification 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2013 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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