Variant rs2404834 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198578.4(LRRK2):c.5948+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,594,976 control chromosomes in the GnomAD database, including 16,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1713 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14895 hom. )

Consequence

LRRK2
NM_198578.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.520

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-40335205-C-T is Benign according to our data. Variant chr12-40335205-C-T is described in ClinVar as [Benign]. Clinvar id is 1250743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK2	NM_198578.4 linkuse as main transcript	c.5948+48C>T		intron_variant		ENST00000298910.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2	ENST00000298910.12 linkuse as main transcript	c.5948+48C>T		intron_variant		1	NM_198578.4	P1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21385

AN:

151990

Hom.:

1710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.0931

Gnomad ASJ

AF:

0.0720

Gnomad EAS

AF:

0.0258

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.122

AC:

29498

AN:

242070

Hom.:

2279

AF XY:

0.119

AC XY:

15584

AN XY:

130812

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.0790

Gnomad ASJ exome

AF:

0.0697

Gnomad EAS exome

AF:

0.0261

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.136

AC:

196946

AN:

1442868

Hom.:

14895

Cov.:

AF XY:

0.134

AC XY:

96050

AN XY:

718286

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0794

Gnomad4 ASJ exome

AF:

0.0698

Gnomad4 EAS exome

AF:

0.0301

Gnomad4 SAS exome

AF:

0.0390

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.141

AC:

21397

AN:

152108

Hom.:

1713

Cov.:

AF XY:

0.143

AC XY:

10659

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0928

Gnomad4 ASJ

AF:

0.0720

Gnomad4 EAS

AF:

0.0261

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.133

Hom.:

1552

Bravo

AF:

0.129

Asia WGS

AF:

0.0440

AC:

155

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.35

DANN

Benign

0.71

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