rs141252946
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7
The NM_198578.4(LRRK2):c.3033G>A(p.Glu1011=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
LRRK2
NM_198578.4 synonymous
NM_198578.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.94
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 12-40295581-G-A is Benign according to our data. Variant chr12-40295581-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1799066.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.94 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRK2 | NM_198578.4 | c.3033G>A | p.Glu1011= | synonymous_variant | 23/51 | ENST00000298910.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000298910.12 | c.3033G>A | p.Glu1011= | synonymous_variant | 23/51 | 1 | NM_198578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250868Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135568
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461730Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727164
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74466
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at