12-40225191-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_198578.4(LRRK2):c.60A>G(p.Ile20Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I20I) has been classified as Likely benign.
Frequency
Consequence
NM_198578.4 missense
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.60A>G | p.Ile20Met | missense_variant | 1/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.60A>G | p.Ile20Met | missense_variant | 1/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461864Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727234
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 02, 2022 | The p.I20M variant (also known as c.60A>G), located in coding exon 1 of the LRRK2 gene, results from an A to G substitution at nucleotide position 60. The isoleucine at codon 20 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.