8-144359409-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001363118.2(SLC52A2):c.116A>G(p.Lys39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,611,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001363118.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC52A2 | NM_001363118.2 | c.116A>G | p.Lys39Arg | missense_variant | Exon 2 of 5 | ENST00000643944.2 | NP_001350047.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000199 AC: 3AN: 150408Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 249772Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135292
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461484Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727048
GnomAD4 genome AF: 0.0000199 AC: 3AN: 150512Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1AN XY: 73502
ClinVar
Submissions by phenotype
Brown-Vialetto-van Laere syndrome 2 Uncertain:2
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This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 39 of the SLC52A2 protein (p.Lys39Arg). This variant is present in population databases (rs782174760, gnomAD 0.007%). 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: 579817). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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
The c.116A>G (p.K39R) alteration is located in exon 2 (coding exon 1) of the SLC52A2 gene. This alteration results from a A to G substitution at nucleotide position 116, causing the lysine (K) at amino acid position 39 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at