rs33962975
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_198578.4(LRRK2):āc.7155A>Gā(p.Gly2385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,611,208 control chromosomes in the GnomAD database, including 16,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.11 ( 1252 hom., cov: 32)
Exomes š: 0.13 ( 14824 hom. )
Consequence
LRRK2
NM_198578.4 synonymous
NM_198578.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.34
Genes affected
LRRK2 (HGNC:18618): (leucine rich repeat kinase 2) This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 12-40363528-A-G is Benign according to our data. Variant chr12-40363528-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 39234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-40363528-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.34 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.7155A>G | p.Gly2385= | synonymous_variant | 48/51 | ENST00000298910.12 | |
LOC105369736 | XR_944868.3 | n.485-8701T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.7155A>G | p.Gly2385= | synonymous_variant | 48/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.109 AC: 16574AN: 151864Hom.: 1250 Cov.: 32
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GnomAD3 exomes AF: 0.113 AC: 28221AN: 250616Hom.: 2177 AF XY: 0.112 AC XY: 15158AN XY: 135478
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GnomAD4 exome AF: 0.134 AC: 195465AN: 1459226Hom.: 14824 Cov.: 34 AF XY: 0.132 AC XY: 95495AN XY: 725966
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GnomAD4 genome ? AF: 0.109 AC: 16586AN: 151982Hom.: 1252 Cov.: 32 AF XY: 0.111 AC XY: 8278AN XY: 74296
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal dominant Parkinson disease 8 Benign:3Other:1
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 provided, no classification provided | literature only | GeneReviews | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 22, 2021 | - - |
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 | Athena Diagnostics | Aug 11, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at