rs10878405

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_198578.4(LRRK2):c.6324G>A(p.Glu2108Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,607,610 control chromosomes in the GnomAD database, including 80,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6173 hom., cov: 33)

Exomes 𝑓: 0.31 ( 73852 hom. )

Consequence

LRRK2
NM_198578.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 3.27

Variant links:

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]

LRRK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 12-40348452-G-A is Benign according to our data. Variant chr12-40348452-G-A is described in ClinVar as [Benign]. Clinvar id is 39222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-40348452-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK2	NM_198578.4 link	c.6324G>A	p.Glu2108Glu	synonymous_variant	Exon 43 of 51	ENST00000298910.12	NP_940980.4	Q5S007Q17RV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000298910.12 link	c.6324G>A	p.Glu2108Glu	synonymous_variant	Exon 43 of 51	1	NM_198578.4	ENSP00000298910.7		Q5S007

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41286

AN:

151872

Hom.:

6171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.264

GnomAD3 exomes

AF:

0.302

AC:

75665

AN:

250916

Hom.:

12165

AF XY:

0.309

AC XY:

41856

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.362

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.313

AC:

456015

AN:

1455620

Hom.:

73852

Cov.:

AF XY:

0.315

AC XY:

228474

AN XY:

724384

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.274

Gnomad4 EAS exome

AF:

0.320

Gnomad4 SAS exome

AF:

0.360

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.272

AC:

41305

AN:

151990

Hom.:

6173

Cov.:

AF XY:

0.278

AC XY:

20613

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.341

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.324

Gnomad4 OTH

AF:

0.266

Alfa

AF:

0.301

Hom.:

9463

Bravo

AF:

0.253

Asia WGS

AF:

0.337

AC:

1167

AN:

3472

EpiCase

AF:

0.305

EpiControl

AF:

0.310

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant Parkinson disease 8

Benign:3Other:1

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 22, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.6

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over