rs34637584

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 9P and 1B. PP3PP5_Very_StrongBP4

The NM_198578.4(LRRK2):c.6055G>A(p.Gly2019Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,613,804 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic,risk factor (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

LRRK2
NM_198578.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic; risk factor criteria provided, multiple submitters, no conflicts P:25O:2

Conservation

PhyloP100: 9.66

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 Likely_pathogenic. Variant got 8 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 11: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

PP5

Variant 12-40340400-G-A is Pathogenic according to our data. Variant chr12-40340400-G-A is described in ClinVar as [Likely_pathogenic, risk_factor]. Clinvar id is 1940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-40340400-G-A is described in Lovd as [Pathogenic]. Variant chr12-40340400-G-A is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.15880463). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRK2	NM_198578.4 link	c.6055G>A	p.Gly2019Ser	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
LRRK2	ENST00000298910.12 link	c.6055G>A	p.Gly2019Ser	missense_variant	Exon 41 of 51	1	NM_198578.4	ENSP00000298910.7		Q5S007

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000526

AC:

132

AN:

251154

Hom.:

AF XY:

0.000553

AC XY:

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00854

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000417

AC:

609

AN:

1461622

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

300

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00785

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000361

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000773

Hom.:

Bravo

AF:

0.000586

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000387

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Pathogenic/Likely pathogenic; risk factor

Submissions summary: Pathogenic:25Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant Parkinson disease 8

Pathogenic:14Other:1

Apr 28, 2022

Genetics and Molecular Pathology, SA Pathology

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 14, 2014

Courtagen Diagnostics Laboratory, Courtagen Life Sciences

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 08, 2023

Clinical Genomics Laboratory, Washington University in St. Louis

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The LRRK2 c.6055G>A (p.Gly2019Ser) variant is reported as one of the most common alleles in individuals affected with Parkinson‚Äôs disease and segregates with disease in families (Saunders-Pullman R et al., PMID: 20301387). The highest population minor allele frequency in the population database genome aggregation database (v.2.1.1) is 0.84% in Ashkenazi Jewish population. Functional studies show increased mitochondrial DNA damage, increased phosphorylation of alpha synuclein, dysregulation of lysosomal function, and kinase-dependent neurodegeneration (Henry G et al., PMID: 26251043; Qing H et al., PMID: 19576176; Sanders LH et al., PMID: 24148854; Vermilyea SC et al., PMID: 29402177), indicating that this variant impacts protein function. This variant resides within a region, amino acids 1879-2138, of LRRK2 that is defined as a critical functional domain (Vermilyea SC et al., PMID: 29402177). Computational predictors indicate that the variant is damaging, evidence that correlates with impact to LRRK2 function. This variant has been reported in the ClinVar database as a pathogenic variant in Parkinson‚Äôs disease by 18 submitters, likely pathogenic by one submitter and a risk factor by one submitter. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as pathogenic. -

Aug 02, 2021

Illumina Laboratory Services, Illumina

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The LRRK2 c.6055G>A (p.Gly2019Ser) missense variant is the most common variant reported in individuals with LRRK2-related Parkinson disease (PD) (Saunders-Pullman et al. 2006). Across a selection of available literature, the p.Gly2019Ser variant has been identified in a heterozygous state in 131 individuals and in a homozygous state in two individuals with Parkinson disease (Kachergus et al. 2005; Nichols et al. 2005; Bar-Shira et al. 2009). The p.Gly2019Ser variant was absent from 3487 healthy matched controls in these studies and is reported at a frequency of 0.008396 in the Ashkenazi Jewish population of the Genome Aggregation Database (version 2.1.1). Analysis showed that carriers of the p.Gly2019Ser variant, who were of Ashkenazi Jewish descent, shared a 243 kb haplotype, suggesting a common founder in this population (Bar-Shira et al. 2009). The variant is also noted to exist as a founder variant in North African Berbers (Saunders-Pullman et al. 2006). The p.Gly2019Ser variant is associated with reduced penetrance; penetrance for heterozygotes is age dependent, and varies in different populations ranging from 25% - 42% up to age 80 (Saunders-Pullman et al. 2006). Generally clinical features are indistinguishable between individuals with LRRK2-related PD compared to idiopathic PD. However, studies have shown the p.Gly2019Ser variant results in a slightly milder clinical course than seen in individuals with Parkinson disease (Saunders-Pullman et al. 2006). Mitochondrial dysfunction and lysosomal dysfunction play central roles in PD pathophysiology. Functional studies showed increased mitochondrial DNA damage in iPSC-derived neural cells from patients carrying the p.Gly2019Ser variant than in cells from healthy controls. In patient cells in which the p.Gly2019Ser variant was repaired with zinc finger nuclease, reduced mitochondrial DNA damage was observed at levels seen in healthy control cells (Sanders et al. 2014). The p.Gly2019Ser variant has also been demonstrated to result in enlarged lysosomes, impaired lysosomal function, and increased kinase activity (Henry et al. 2015). Based on the collective evidence, the p.Gly2019Ser variant is classified as pathogenic for LRRK2-related Parkinson disease. -

Dec 07, 2017

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 22, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 22, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: LRRK2 c.6055G>A (p.Gly2019Ser) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00053 in 251154 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in LRRK2 causing Parkinson Disease 8, Autosomal Dominant, allowing no conclusion about variant significance. c.6055G>A has been widely reported in the literature in multiple individuals affected with Parkinson Disease 8, Autosomal Dominant as a common founder mutation associated with age dependent penetrance among European populations (example, Kachergus_2005) and this association continues to be subsequently acknowledged and cited by others. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (example, Greggio_2006). The most pronounced variant effect results in increased tendency to form inclusion bodies. Secondly, neurons and neuronal cell lines undergo cell death after expression of mutant protein. Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

Nov 14, 2023

3billion

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.112%). Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000001421 /PMID: 16311595). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. -

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Jan 23, 2020

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. -

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2019 of the LRRK2 protein (p.Gly2019Ser). This variant is present in population databases (rs34637584, gnomAD 0.9%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Parkinson‚Äôs disease (PD) and is one of the most common known genetic causes of PD. This variant has been reported to have a reduced penetrance of 25-42.5% in various populations (PMID: 15680455, 15726496, 18986508, 22575234, 26062626, 28639421). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1940). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LRRK2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects LRRK2 function (PMID: 26251043). For these reasons, this variant has been classified as Pathogenic. -

Jan 06, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 06, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Pathogenic:7

Mar 12, 2020

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The G2019S variant is the most common pathogenic substitution in the LRRK2 gene (Lunati et al., 2018); Individuals who are heterozygous for the G2019S variant have more than a 20-fold increase in risk for developing Parkinson disease (Dachsel et al., 2010); Lysosomal dysfunction plays a central role in the pathogenesis of Parkinson disease, and published functional studies have shown that expression of G2019S produces enlarged lysosomes and alters their function (Henry et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24211199, 19397894, 22080837, 21362567, 15726496, 29357897, 29248340, 30528841, 22736029, 23241358, 23396536, 20232069, 21280089, 20008657, 22914360, 21961647, 20642453, 17447891, 21686713, 22539006, 22773119, 23357204, 23472874, 21658387, 24729340, 19072560, 24652679, 21699405, 17200152, 21972245, 24470158, 21850687, 23227859, 19302196, 22004453, 20626563, 20881132, 25401981, 25330418, 22194196, 17210620, 21885347, 24488318, 24357540, 20818610, 22488887, 21696411, 21883375, 20671708, 23075850, 20096956, 16750377, 24148854, 18675914, 23747310, 25107341, 17095157, 19283415, 21753159, 22323743, 22914834, 25008396, 21494637, 23082216, 21390248, 21799870, 24082139, 22689969, 23764467, 18752982, 19945904, 20933457, 21641848, 22575234, 25434972, 23241745, 25000966, 26251043, 20457952, 18986508, 27692902, 27383589, 27423549, 27393345, 24360742, 24243757, 25962553, 23664753, 26159606, 26282470, 28862745, 29309488, 29800472, 30245141, 30709905, 3066573, 30146349, 16333314, 28487191, 28723952, 16102999, 16001413, 28639421, 18644660, 24123150, 19741132, 30172844, 16966501, 17060589, 29795570, 17116211, 24282027, 30665703, 31077434, 31324919, 31813996, 31605779, 31980526, 32875616, 26600626, 32398759, 33281709, 32353202, 18201824, 33084218, 15852371, 31589614) -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 18, 2024

Athena Diagnostics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This variant is reported to exhibit age-dependent penetrance that may be impacted by ethnicity (PMID: 26062626, 25330418, 18986508). This variant appears to be associated with disease in multiple families (PMID: 16240353, 16533964). According to published literature, there is no reported difference in clinical presentation between individuals with this variant in the heterozygous or homozygous state (PMID: 16966502). Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 29402177, 29386392, 26251043, 23472874, 27413152, 35732218) -

Oct 23, 2020

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 24, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LRRK2: PS4, PM1, PP1:Moderate, PP3, PS3:Supporting -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Parkinson disease, late-onset

Pathogenic:1

May 03, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Pathogenic:1

Jul 19, 2022

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.6055G>A (p.G2019S) alteration is located in exon 41 (coding exon 41) of the LRRK2 gene. This alteration results from a G to A substitution at nucleotide position 6055, causing the glycine (G) at amino acid position 2019 to be replaced by a serine (S). Based on data from gnomAD, the A allele has an overall frequency of 0.05% (138/282542) total alleles studied. The highest observed frequency was 0.84% (87/10362) of Ashkenazi Jewish alleles. The p.G2019S alteration is the most common disease-causing LRRK2 alteration (Saunders-Pullman, 2019). This amino acid position is highly conserved in available vertebrate species. Functional analysis demonstrated that compared to the wild-type, the p.G2019S alteration significantly increased the phosphorylation of peroxiredoxin 3 (PRDX3), a mitochondrial member of the antioxidant family of thioredoxin peroxidases. Increased PRDX3 phosphorylation was associated with inhibited PRDX3 peroxidase activity and increased death in LRRK2-expressing but not in LRRK2-depleted or vector-transfected neuronal cells (Angeles, 2011). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. -

Parkinson disease

Pathogenic:1

Mar 30, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change in LRRK2 is predicted to replace glycine with serine at codon 2019, p.(Gly2019Ser). The glycine residue is highly conserved (100 vertebrates, UCSC), and is located in the protein kinase domain There is a small physicochemical difference between glycine and serine. The highest population minor allele frequency in gnomAD v2.1 is 0.8% (87/10,362 alleles, 1 homozygote) in the Ashkenazi Jewish population, while the highest continental population minor allele frequency is 0.03% (33/128,908 alleles) in the European (non-Finnish) population. This is the most commonly reported pathogenic variant in LRRK2 and is associated with a risk of Parkinson disease (PD) at an estimated age-related penetrance of between 25-42.5% (PMID: 20301387, 28639421). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (odds ratio 14.98, 95% CI:10.68-21.02) (PMID: 22575234). The variant has been reported to segregate with PD in multiple families (PMID: 15726496 ). A transgenic mouse model for the variant recapitulates the human PD phenotype and brain histopathology (PMID: 22539006). Multiple lines of computational evidence predict a deleterious effect for the missense substitution (6/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as PATHOGENIC. Following criteria are met: PS3, PP1_Strong, PS4_Moderate, PP3. -

LRRK2-related disorder

Pathogenic:1

Sep 04, 2024

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The LRRK2 c.6055G>A variant is predicted to result in the amino acid substitution p.Gly2019Ser. This variant has been found in patients with Parkinson disease and is the most common and well-documented pathogenic variant in the LRRK2 gene (Trinh et al. 2016. PubMed ID: 27692902; Biosa et al. 2013. PubMed ID: 23241358; Bonifati et al. 2006. PubMed ID: 16835587). This variant is reported in 0.84% of alleles in individuals of Ashkenazi Jewish descent in gnomAD and it has been reported as a founder mutation in this population (Bar-Shira et al. 2009. PubMed ID: 19283415). Functional studies showed that this variant activated kinase activity, enlarged lysosomes and diminished the lysosomal capacity (Jaleel et al. 2007. PubMed ID: 17447891; West et al. 2007. PubMed ID: 17200152; Henry et al. 2015. PubMed ID: 26251043). This variant is interpreted as pathogenic. -

Young-onset Parkinson disease

Other:1

Dec 29, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: risk factor

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LRRK2 c.6055G>A (p.Gly2019Ser) has been associated with increased risk for Parkinson's disease. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of Ashkenazi Jewish ancestry (0.86%, Genome Aggregation Database (gnomAD); rs6025) and is present in ClinVar (ID: 1940). A large meta-analysis has reported an odds ratio of 14.98 [95% CI 4.8-10] for developing Parkinson's disease (Wu 2012). In vivo and in vitro functional studies provide some evidence that the p.Gly2019Ser variant may impact protein function (Chen 2012). Therefore, this variant is not expected to cause highly penetrant Mendelian disease. In summary, this variant is an established risk factor for Parkinson's disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.57

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.16

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.2

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.1

REVEL

Pathogenic

0.97

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MVP

0.98

MPC

1.8

ClinPred

0.18

GERP RS

5.7

Varity_R

0.88

gMVP

0.92

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