rs11175655

Variant names:

• chr12-40229925-G-A
• rs11175655
• NM_198578.4:c.238-2349G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-40229925-G-A
• chr12-40229925-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198578.4(LRRK2):​c.238-2349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 141,882 control chromosomes in the GnomAD database, including 983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (983 hom., cov: 31)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant Parkinson disease 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hereditary late onset Parkinson disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289310 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK2	NM_198578.4	c.238-2349G>A		intron_variant	Intron 2 of 50	ENST00000298910.12	NP_940980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000298910.12	c.238-2349G>A		intron_variant	Intron 2 of 50	1	NM_198578.4	ENSP00000298910.7

Frequencies

GnomAD3 genomes AF: 0.103 AC: 14599 AN: 141848 Hom.: 978 Cov.: 31

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.0730

Gnomad EAS AF: 0.00229

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0793

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 14627 AN: 141882 Hom.: 983 Cov.: 31 AF XY: 0.101 AC XY: 6945 AN XY: 68438

African (AFR) AF: 0.0912 AC: 3587 AN: 39336

American (AMR) AF: 0.0812 AC: 1153 AN: 14200

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 246 AN: 3368

East Asian (EAS) AF: 0.00230 AC: 10 AN: 4352

South Asian (SAS) AF: 0.166 AC: 699 AN: 4204

European-Finnish (FIN) AF: 0.0793 AC: 615 AN: 7756

Middle Eastern (MID) AF: 0.0410 AC: 10 AN: 244

European-Non Finnish (NFE) AF: 0.122 AC: 7989 AN: 65578

Other (OTH) AF: 0.0874 AC: 171 AN: 1956

Alfa AF: 0.113 Hom.: 1890

Bravo AF: 0.0938

Asia WGS AF: 0.0760 AC: 262 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11175655; hg19: chr12-40623727;