rs1555187766
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_198578.4(LRRK2):c.4417C>T(p.Leu1473Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,784 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1473P) has been classified as Uncertain significance.
Frequency
Consequence
NM_198578.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.4417C>T | p.Leu1473Phe | missense_variant | 31/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.4417C>T | p.Leu1473Phe | missense_variant | 31/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727194
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2017 | 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with LRRK2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 1473 of the LRRK2 protein (p.Leu1473Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 19, 2020 | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at