12-40294893-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_198578.4(LRRK2):āc.2857T>Cā(p.Leu953=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,543,352 control chromosomes in the GnomAD database, including 9,795 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. L953L) has been classified as Likely benign.
Frequency
Consequence
NM_198578.4 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.2857T>C | p.Leu953= | synonymous_variant | 22/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.2857T>C | p.Leu953= | synonymous_variant | 22/51 | 1 | NM_198578.4 | P1 | |
LRRK2 | ENST00000680790.1 | c.2602T>C | p.Leu868= | synonymous_variant | 20/49 | ||||
LRRK2 | ENST00000343742.6 | c.2857T>C | p.Leu953= | synonymous_variant | 22/27 | 5 | |||
LRRK2 | ENST00000679360.1 | c.*1766T>C | 3_prime_UTR_variant, NMD_transcript_variant | 23/51 |
Frequencies
GnomAD3 genomes AF: 0.0916 AC: 13926AN: 151954Hom.: 796 Cov.: 32
GnomAD3 exomes AF: 0.104 AC: 26057AN: 249754Hom.: 1522 AF XY: 0.105 AC XY: 14239AN XY: 135140
GnomAD4 exome AF: 0.109 AC: 151772AN: 1391280Hom.: 8999 Cov.: 24 AF XY: 0.108 AC XY: 75102AN XY: 694816
GnomAD4 genome AF: 0.0916 AC: 13932AN: 152072Hom.: 796 Cov.: 32 AF XY: 0.0897 AC XY: 6669AN XY: 74352
ClinVar
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Benign:3Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 29, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 14, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at