rs766491800
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_002294.3(LAMP2):āc.443A>Gā(p.Asn148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,202,195 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002294.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.443A>G | p.Asn148Ser | missense_variant | 4/9 | ENST00000200639.9 | NP_002285.1 | |
LAMP2 | NM_001122606.1 | c.443A>G | p.Asn148Ser | missense_variant | 4/9 | NP_001116078.1 | ||
LAMP2 | NM_013995.2 | c.443A>G | p.Asn148Ser | missense_variant | 4/9 | NP_054701.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000533 AC: 6AN: 112554Hom.: 0 Cov.: 23 AF XY: 0.0000288 AC XY: 1AN XY: 34686
GnomAD3 exomes AF: 0.0000164 AC: 3AN: 182411Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 66985
GnomAD4 exome AF: 0.00000734 AC: 8AN: 1089641Hom.: 0 Cov.: 28 AF XY: 0.00000845 AC XY: 3AN XY: 355229
GnomAD4 genome AF: 0.0000533 AC: 6AN: 112554Hom.: 0 Cov.: 23 AF XY: 0.0000288 AC XY: 1AN XY: 34686
ClinVar
Submissions by phenotype
Danon disease Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 29, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 148 of the LAMP2 protein (p.Asn148Ser). This variant is present in population databases (rs766491800, gnomAD 0.004%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 578311). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 11, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2019 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at