chr12-40235634-T-C
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_198578.4(LRRK2):āc.356T>Cā(p.Leu119Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00182 in 1,602,432 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L119F) has been classified as Uncertain significance.
Frequency
Consequence
NM_198578.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.356T>C | p.Leu119Pro | missense_variant | 4/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.356T>C | p.Leu119Pro | missense_variant | 4/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00137 AC: 209AN: 152242Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00125 AC: 313AN: 251148Hom.: 0 AF XY: 0.00136 AC XY: 185AN XY: 135772
GnomAD4 exome AF: 0.00187 AC: 2713AN: 1450072Hom.: 4 Cov.: 29 AF XY: 0.00184 AC XY: 1329AN XY: 722338
GnomAD4 genome AF: 0.00137 AC: 209AN: 152360Hom.: 0 Cov.: 32 AF XY: 0.00128 AC XY: 95AN XY: 74504
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Benign:2Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | LRRK2: BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 2022 | Reported previously in individuals with Parkinson disease, however L119P was also seen in control subjects (Jasinska-Myga et al., 2010; Ross et al., 2011; Benitez et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28130640, 25466404, 31980526, 33836114, 31996268, 29369408, 27393345, 32557143, 28842327, 20721913, 25174650, 27294386, 21885347, 27094865, 34542912, Kalogeropulou2022[functionalstudy], 33454605) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at