12-40320043-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_198578.4(LRRK2):c.4883G>A(p.Arg1628His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,611,680 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1628P) has been classified as Uncertain significance.
Frequency
Consequence
NM_198578.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.4883G>A | p.Arg1628His | missense_variant | 34/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.4883G>A | p.Arg1628His | missense_variant | 34/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 151994Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000160 AC: 40AN: 250278Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135420
GnomAD4 exome AF: 0.000112 AC: 163AN: 1459568Hom.: 0 Cov.: 36 AF XY: 0.0000992 AC XY: 72AN XY: 726076
GnomAD4 genome AF: 0.000112 AC: 17AN: 152112Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 25, 2019 | - - |
Autosomal dominant Parkinson disease 8 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at