rs10784486

chr12-40283227-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198578.4(LRRK2):c.2242-648A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 151,994 control chromosomes in the GnomAD database, including 37,802 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 0.70 (37802 hom., cov: 31)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRK2	NM_198578.4	c.2242-648A>C		intron_variant		ENST00000298910.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRK2	ENST00000298910.12	c.2242-648A>C		intron_variant		1	NM_198578.4	P1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106849 AN: 151876 Hom.: 37768 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.704 AC: 106938 AN: 151994 Hom.: 37802 Cov.: 31 AF XY: 0.709 AC XY: 52694 AN XY: 74282

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.684

Alfa AF: 0.675 Hom.: 57476

Bravo AF: 0.696

Asia WGS AF: 0.632 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	7.3
Dann	Benign	0.81

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

Other links and lift over

dbSNP: rs10784486; hg19: chr12-40677029;