chr12-40263898-C-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_198578.4(LRRK2):āc.1653C>Gā(p.Asn551Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 1,596,920 control chromosomes in the GnomAD database, including 5,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. N551N) has been classified as Likely benign.
Frequency
Consequence
NM_198578.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.1653C>G | p.Asn551Lys | missense_variant | 14/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.1653C>G | p.Asn551Lys | missense_variant | 14/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0976 AC: 14840AN: 152000Hom.: 888 Cov.: 32
GnomAD3 exomes AF: 0.0868 AC: 21777AN: 250972Hom.: 1184 AF XY: 0.0806 AC XY: 10935AN XY: 135682
GnomAD4 exome AF: 0.0717 AC: 103567AN: 1444802Hom.: 4312 Cov.: 28 AF XY: 0.0701 AC XY: 50487AN XY: 719822
GnomAD4 genome AF: 0.0977 AC: 14861AN: 152118Hom.: 892 Cov.: 32 AF XY: 0.0984 AC XY: 7319AN XY: 74356
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Benign:3Other:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2018 | This variant is associated with the following publications: (PMID: 31487119, 31182772, 30917570, 29321258, 20186690, 23913756, 20721913) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 29, 2017 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at