rs74985840
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000298910.12(LRRK2):c.3451G>A(p.Ala1151Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).
Frequency
Consequence
ENST00000298910.12 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.3451G>A | p.Ala1151Thr | missense_variant | 25/51 | ENST00000298910.12 | NP_940980.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.3451G>A | p.Ala1151Thr | missense_variant | 25/51 | 1 | NM_198578.4 | ENSP00000298910 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 151916Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251314Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135830
GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461506Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727058
GnomAD4 genome AF: 0.000105 AC: 16AN: 151916Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 9AN XY: 74158
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Uncertain:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 17, 2023 | 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. Experimental studies have shown that this missense change does not substantially affect LRRK2 function (PMID: 20642453). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 39165). This missense change has been observed in individual(s) with Parkinson disease (PMID: 16788020, 21885347, 23963289). This variant is present in population databases (rs74985840, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1151 of the LRRK2 protein (p.Ala1151Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at