rs397516741
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002294.3(LAMP2):c.299C>T(p.Ala100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,207,540 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A100A) has been classified as Likely benign.
Frequency
Consequence
NM_002294.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.299C>T | p.Ala100Val | missense_variant | 3/9 | ENST00000200639.9 | |
LAMP2 | NM_001122606.1 | c.299C>T | p.Ala100Val | missense_variant | 3/9 | ||
LAMP2 | NM_013995.2 | c.299C>T | p.Ala100Val | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.299C>T | p.Ala100Val | missense_variant | 3/9 | 1 | NM_002294.3 | P3 | |
LAMP2 | ENST00000434600.6 | c.299C>T | p.Ala100Val | missense_variant | 3/9 | 1 | A1 | ||
LAMP2 | ENST00000371335.4 | c.299C>T | p.Ala100Val | missense_variant | 3/9 | 1 | A1 | ||
LAMP2 | ENST00000706600.1 | c.299C>T | p.Ala100Val | missense_variant | 3/9 |
Frequencies
GnomAD3 genomes ? AF: 0.0000451 AC: 5AN: 110897Hom.: 0 Cov.: 20 AF XY: 0.0000906 AC XY: 3AN XY: 33121
GnomAD3 exomes AF: 0.0000491 AC: 9AN: 183472Hom.: 0 AF XY: 0.0000736 AC XY: 5AN XY: 67916
GnomAD4 exome AF: 0.0000492 AC: 54AN: 1096590Hom.: 0 Cov.: 30 AF XY: 0.0000359 AC XY: 13AN XY: 361970
GnomAD4 genome ? AF: 0.0000451 AC: 5AN: 110950Hom.: 0 Cov.: 20 AF XY: 0.0000904 AC XY: 3AN XY: 33184
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 11, 2012 | Ala100Val in 3 of LAMP2: This variant is not expected to have clinical significa nce because it has been previously reported in a phenotypically unaffected male who was hemizygous for this variant. Ala100Val in 3 of LAMP2 (allele frequency = n/a) - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 14, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Danon disease Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 17, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | LAMP2: BP4, BS2 - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2019 | 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