chr12-40224903-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000416796.5(LRRK2):c.-62-652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 579,948 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0097 ( 25 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 13 hom. )
Consequence
LRRK2
ENST00000416796.5 intron
ENST00000416796.5 intron
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.18
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 12-40224903-G-A is Benign according to our data. Variant chr12-40224903-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196141.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00974 (1484/152336) while in subpopulation AFR AF= 0.0337 (1403/41572). AF 95% confidence interval is 0.0323. There are 25 homozygotes in gnomad4. There are 690 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1478 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRK2 | ENST00000416796.5 | c.-62-652G>A | intron_variant | 3 | |||||
LRRK2-DT | ENST00000618127.1 | n.13C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.00971 AC: 1478AN: 152230Hom.: 25 Cov.: 33
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GnomAD4 exome AF: 0.00113 AC: 485AN: 427612Hom.: 13 Cov.: 4 AF XY: 0.000938 AC XY: 214AN XY: 228162
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GnomAD4 genome ? AF: 0.00974 AC: 1484AN: 152336Hom.: 25 Cov.: 33 AF XY: 0.00926 AC XY: 690AN XY: 74490
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 11, 2018 | - - |
Computational scores
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Name
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at