rs201673476
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001363118.2(SLC52A2):c.1277C>T(p.Pro426Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,613,536 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P426S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001363118.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A2 | NM_001363118.2 | c.1277C>T | p.Pro426Leu | missense_variant | 5/5 | ENST00000643944.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A2 | ENST00000643944.2 | c.1277C>T | p.Pro426Leu | missense_variant | 5/5 | NM_001363118.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152178Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251208Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135874
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461240Hom.: 1 Cov.: 35 AF XY: 0.0000509 AC XY: 37AN XY: 726932
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74476
ClinVar
Submissions by phenotype
Brown-Vialetto-van Laere syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 426 of the SLC52A2 protein (p.Pro426Leu). This variant is present in population databases (rs201673476, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SLC52A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 540436). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC52A2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 20, 2020 | The p.P426L variant (also known as c.1277C>T), located in coding exon 4 of the SLC52A2 gene, results from a C to T substitution at nucleotide position 1277. The proline at codon 426 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at