rs78029637

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198578.4(LRRK2):​c.6091A>C​(p.Thr2031Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

LRRK2
NM_198578.4 missense

Scores

2
12
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.96
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRK2NM_198578.4 linkc.6091A>C p.Thr2031Pro missense_variant Exon 41 of 51 ENST00000298910.12 NP_940980.4 Q5S007Q17RV3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRK2ENST00000298910.12 linkc.6091A>C p.Thr2031Pro missense_variant Exon 41 of 51 1 NM_198578.4 ENSP00000298910.7 Q5S007

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461550
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.65
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.064
D
MetaRNN
Uncertain
0.70
D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.35
Sift
Uncertain
0.026
D
Sift4G
Uncertain
0.0070
D
Polyphen
0.99
D
Vest4
0.50
MutPred
0.73
Gain of catalytic residue at T2031 (P = 0.0648);
MVP
0.90
MPC
2.0
ClinPred
0.97
D
GERP RS
5.7
Varity_R
0.61
gMVP
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-40734238; API