chrX-120456676-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002294.3(LAMP2):c.158G>T(p.Arg53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,030,671 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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. R53C) has been classified as Likely benign.
Frequency
Consequence
NM_002294.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.158G>T | p.Arg53Leu | missense_variant | 2/9 | ENST00000200639.9 | |
LAMP2 | NM_001122606.1 | c.158G>T | p.Arg53Leu | missense_variant | 2/9 | ||
LAMP2 | NM_013995.2 | c.158G>T | p.Arg53Leu | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.158G>T | p.Arg53Leu | missense_variant | 2/9 | 1 | NM_002294.3 | P3 | |
LAMP2 | ENST00000434600.6 | c.158G>T | p.Arg53Leu | missense_variant | 2/9 | 1 | A1 | ||
LAMP2 | ENST00000371335.4 | c.158G>T | p.Arg53Leu | missense_variant | 2/9 | 1 | A1 | ||
LAMP2 | ENST00000706600.1 | c.158G>T | p.Arg53Leu | missense_variant | 2/9 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD4 exome AF: 0.00000291 AC: 3AN: 1030671Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0AN XY: 315889
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
Danon disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 53 of the LAMP2 protein (p.Arg53Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at