12-40364956-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_198578.4(LRRK2):āc.7296C>Gā(p.Gly2432Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000093 in 1,612,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_198578.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 151786Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000136 AC: 34AN: 250828Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135578
GnomAD4 exome AF: 0.0000917 AC: 134AN: 1460584Hom.: 0 Cov.: 32 AF XY: 0.000113 AC XY: 82AN XY: 726612
GnomAD4 genome AF: 0.000105 AC: 16AN: 151786Hom.: 0 Cov.: 33 AF XY: 0.0000674 AC XY: 5AN XY: 74132
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Uncertain:1Benign:1
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Inborn genetic diseases Benign:1
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