rs376015112
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_198578.4(LRRK2):c.2314C>T(p.Arg772Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 1,613,516 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_198578.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.2314C>T | p.Arg772Ter | stop_gained | 19/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.2314C>T | p.Arg772Ter | stop_gained | 19/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151960Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251092Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135674
GnomAD4 exome AF: 0.0000705 AC: 103AN: 1461556Hom.: 0 Cov.: 31 AF XY: 0.0000605 AC XY: 44AN XY: 727060
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151960Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74208
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 16, 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. ClinVar contains an entry for this variant (Variation ID: 236290). This premature translational stop signal has been observed in individual(s) with Parkinson disease (PMID: 26213354). This variant is present in population databases (rs376015112, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg772*) in the LRRK2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LRRK2 cause disease. - |
Uncertain significance, no assertion criteria provided | literature only | GeneReviews | Dec 11, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at