GeneBe

rs398122396

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_001257180.2(SLC20A2):​c.1828_1831delTCCC​(p.Ser610AlafsTer18) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC20A2
NM_001257180.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 10.0

Publications

3 publications found
Variant links:
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]
SLC20A2 Gene-Disease associations (from GenCC):
  • basal ganglia calcification, idiopathic, 1
    Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • bilateral striopallidodentate calcinosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-42417930-CGGGA-C is Pathogenic according to our data. Variant chr8-42417930-CGGGA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 75231.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC20A2NM_001257180.2 linkc.1828_1831delTCCC p.Ser610AlafsTer18 frameshift_variant Exon 11 of 11 ENST00000520262.6 NP_001244109.1 Q08357A0A384MR38

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC20A2ENST00000520262.6 linkc.1828_1831delTCCC p.Ser610AlafsTer18 frameshift_variant Exon 11 of 11 2 NM_001257180.2 ENSP00000429754.1 Q08357

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461612
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
727114
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33468
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53380
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111848
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome 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
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SLC20A2-related disorder Pathogenic:1
Jul 31, 2024
PreventionGenetics, part of Exact Sciences
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing

The SLC20A2 c.1828_1831delTCCC variant is predicted to result in a frameshift and premature protein termination (p.Ser610Alafs*18). This variant occurs within the terminal exon of SLC20A2 and has been reported in nine members of a family presenting with idiopathic basal ganglia calcification (Family F2 in Hsu et al. 2013. PubMed ID: 23334463). Of note, an additional member of family F2 in Hsu et al. was reported as affected but did not have the variant. This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in SLC20A2 are expected to be pathogenic and another truncating variant has been documented downstream of p.Ser610 (Hozumi et al. 2018. PubMed ID: 29627011). Based on this evidence, this variant is interpreted as pathogenic. -

Idiopathic basal ganglia calcification 1 Pathogenic:1
Feb 01, 2013
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
10
Mutation Taster
=7/193
disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs398122396; hg19: chr8-42275448; API