chr12-40238297-T-G

Position:

• chr12-40238297-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198578.4(LRRK2):​c.571+194T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,114 control chromosomes in the GnomAD database, including 1,713 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)
• Consequence: LRRK2 NM_198578.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 12-40238297-T-G is Benign according to our data. Variant chr12-40238297-T-G is described in ClinVar as [Benign]. Clinvar id is 1272742.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRK2	NM_198578.4	c.571+194T>G		intron_variant		ENST00000298910.12	NP_940980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRK2	ENST00000298910.12	c.571+194T>G		intron_variant		1	NM_198578.4	ENSP00000298910.7

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21829 AN: 151996 Hom.: 1709 Cov.: 32

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.144 AC: 21844 AN: 152114 Hom.: 1713 Cov.: 32 AF XY: 0.139 AC XY: 10351 AN XY: 74376

Gnomad4 AFR AF: 0.0972

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.136

Alfa AF: 0.176 Hom.: 2562

Bravo AF: 0.138

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
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: rs10878246; hg19: chr12-40632099;