rs797045202
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_001363118.2(SLC52A2):c.1088C>T(p.Pro363Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,452,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P363A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001363118.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A2 | NM_001363118.2 | c.1088C>T | p.Pro363Leu | missense_variant | 4/5 | ENST00000643944.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A2 | ENST00000643944.2 | c.1088C>T | p.Pro363Leu | missense_variant | 4/5 | NM_001363118.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000619 AC: 9AN: 1452854Hom.: 0 Cov.: 45 AF XY: 0.00000553 AC XY: 4AN XY: 723004
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Brown-Vialetto-van Laere syndrome 2 Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2020 | This sequence change replaces proline with leucine at codon 363 of the SLC52A2 protein (p.Pro363Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with a second, rare SLC52A2 variant in an individual affected with  Brown-Vialetto-Van Laere syndrome (PMID: 29053833). ClinVar contains an entry for this variant (Variation ID: 210042). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 13, 2019 | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at