NM_001282225.2:c.506G>A

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 10P and 1B. PM5PP5_Very_StrongBP4

The NM_001282225.2(ADA2):c.506G>A(p.Arg169Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000502 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169W) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

ADA2
NM_001282225.2 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:24O:1

Conservation

PhyloP100: 3.88

Publications

54 publications found

Variant links:

Genes affected

ADA2 (HGNC:1839): (adenosine deaminase 2) This gene encodes a member of a subfamily of the adenosine deaminase protein family. The encoded protein is one of two adenosine deaminases found in humans, which regulate levels of the signaling molecule, adenosine. The encoded protein is secreted from monocytes undergoing differentiation and may regulate cell proliferation and differentiation. This gene may be responsible for some of the phenotypic features associated with cat eye syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ADA2 Gene-Disease associations (from GenCC):

deficiency of adenosine deaminase 2
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
vasculitis due to ADA2 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
polyarteritis nodosa
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
Sneddon syndrome
Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr22-17207108-G-A is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 956376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

PP5

Variant 22-17207107-C-T is Pathogenic according to our data. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17207107-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 120303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.26673746). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA2	NM_001282225.2 link	c.506G>A	p.Arg169Gln	missense_variant	Exon 3 of 10	ENST00000399837.8	NP_001269154.1	Q9NZK5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA2	ENST00000399837.8 link	c.506G>A	p.Arg169Gln	missense_variant	Exon 3 of 10	1	NM_001282225.2	ENSP00000382731.2		Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000558

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000469

AC:

118

AN:

251456

AF XY:

0.000493

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000513

AC:

750

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00187

AC:

100

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000568

AC:

632

AN:

1111988

Other (OTH)

AF:

0.000248

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000394

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000472

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000356

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:24Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:11

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 16, 2021

Genetic Services Laboratory, University of Chicago

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNA sequence analysis of the ADA2 gene demonstrated a sequence change, c.506G>A, in exon 3 that results in an amino acid change, p.Arg169Gln. This sequence change is a well-described pathogenic variant in both the homozygous and compound heterozygous state in individuals with ADA2-related disorders (PMID: 24552285, 28993957, 25457153, 29391253, 32499645, 26922074, 28493328, 30924144, 32353633). This sequence change has been described in the gnomAD database with frequency of 0.19% in the Finnish subpopulation (dbSNP rs77563738). The p.Arg169Gln change affects highly conserved amino acid residue located in a domain of the ADA2 protein that is known to be functional. Although, in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg169Gln substitution, experimental studies have demonstrated that this variant impacts ADA2 activity (PMID: 26867732, 24552285). -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 15, 2022

GeneDx

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Published functional studies demonstrate a damaging effect; R169Q results in decreased ADA2 secretion and activity (Navon et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28830446, 27130863, 29271561, 25457153, 25075846, 25075845, 27663683, 25083540, 25888558, 24552285, 28993957, 24737293, 29736678, 25278816, 28974505, 29681619, 29391253, 29564582, 27059682, 28516235, 28493328, 28805790, 29273180, 29411230, 26867732, 26922074, 27514238, 28522451, 24552284, 30924144, 31393689, 33021335, 30386947, 31980526, 32353633, 33726816, 32499645, 32581362, 33757531, 33517505) -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ADA2: PM1:Strong, PS1, PP1, PP2, PP4, PS3:Supporting -

Apr 24, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PP1, PP3, PM3_strong, PS3_moderate, PS4_moderate -

Jun 10, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The ADA2 c.506G>A; p.Arg169Gln variant (rs77563738; ClinVar Variation ID: 120303) is reported in the literature as homozygous or compound heterozygous in at least twelve probands affected with ADA2-associated disorders and also segregated with at least 9 affected relatives (Elkan 2014, Schepp 2016, Van Eyck 2014, Van Eyck 2015, Van Montfrans 2014, Van Montfrans 2016, Westendorp 2015, Zhou 2014). This variant is found in the general population with an overall allele frequency of 0.05% (134/282,860 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.87). Additionally, functional analyses demonstrate that this variant reduces secretion and activity of the protein encoded by ADA2 (Elkan 2014). Based on the available information, the p.Arg169Gln variant is considered pathogenic. References: Elkan et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014 Mar 6;370(10):921-31. PMID: 24552285. Schepp et al. Deficiency of Adenosine Deaminase 2 Causes Antibody Deficiency. J Clin Immunol. 2016 Apr;36(3):179-86. PMID: 26922074. Van Eyck et al. Hematopoietic stem cell transplantation rescues the immunologic phenotype and prevents vasculopathy in patients with adenosine deaminase 2 deficiency. J Allergy Clin Immunol. 2015 Jan;135(1):283-7.e5. PMID: 25457153. Van Eyck et al. Mutant ADA2 in vasculopathies. N Engl J Med. 2014 Jul 31;371(5):478-9. PMID: 25075848. Van Montfrans et al. Mutant ADA2 in vasculopathies. N Engl J Med. 2014 Jul 31;371(5):478. PMID: 25075845. Van Montfrans et al. Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations. Rheumatology (Oxford). 2016 May;55(5):902-10. PMID: 26867732. Westendorp et al. Unexplained early-onset lacunar stroke and inflammatory skin lesions: Consider ADA2 deficiency. Neurology. 2015 May 19;84(20):2092-3. PMID: 25888558. Zhou et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med. 2014 Mar 6;370(10):911-20. PMID: 24552284. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Vasculitis due to ADA2 deficiency

Pathogenic:8Other:1

Mar 06, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Dec 02, 2020

Johns Hopkins Genomics, Johns Hopkins University

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This ADA2 variant has been identified in numerous patients with ADA2-deficiency in both the compound heterozygous and homozygous state. ADA2 c.506G>A is located within the putative receptor-binding domain and functional studies have demonstrated that this variant causes severely decreased levels of secreted ADA2. This variant has been seen in trans with a second disease-causing ADA2 variant in affected individuals within a family. ADA2 c.506G>A (rs77563738) is present in a large population dataset (gnomAD: 134/282860 total alleles; 0.05%; no homozygotes) and has been reported in ClinVar. Three bioinformatic tools queried predict that this substitution would be damaging, and the arginine residue at this position is highly evolutionarily conserved across most species assessed. We consider this variant to be pathogenic. -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Sep 24, 2024

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 06, 2017

CENTOGENE GmbH and LLC - Guiding Precision Medicine

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the ADA2 protein (p.Arg169Gln). This variant is present in population databases (rs77563738, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with ADA2-related conditions (PMID: 24552284, 24552285, 25888558, 26867732). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 120303). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ADA2 protein function. Experimental studies have shown that this missense change affects ADA2 function (PMID: 24552285, 26867732). For these reasons, this variant has been classified as Pathogenic. -

Nov 24, 2020

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

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: CECR1 c.506G>A (p.Arg169Gln) results in a conservative amino acid change in the encoded protein sequence. CECR1 is also known as ADA2 in the literature and databases. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00047 in 251456 control chromosomes (gnomAD). c.506G>A has been reported (in both homozygous and compound heterozygous states) in the literature in individuals affected with Polyarteritis Nodosa, Childhoood-Onset (e.g. Elkan_2014, Zhou_2014) and ADA2-deficiency (e.g. VanMontfrans_2016). In many families, the variant was reported to segregate with disease. These data indicate that the variant is very likely to be associated with disease. In functional studies performed in both patient-derived cells and in cells transfected with the variant, c.506G>A resulted in reduced enzymatic activity as well as reduced protein secretion (e.g. VanMontfrans_2016, Elkan_2014). Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. -

Genomics England Pilot Project, Genomics England

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2022

Baylor Genetics

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sneddon syndrome;C3887654:Vasculitis due to ADA2 deficiency

Pathogenic:1

Apr 29, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammatory syndrome

Pathogenic:1

Feb 17, 2017

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inherited Immunodeficiency Diseases

Pathogenic:1

Jan 01, 2019

NIHR Bioresource Rare Diseases, University of Cambridge

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

ADA2-related disorder

Pathogenic:1

Sep 06, 2024

PreventionGenetics, part of Exact Sciences

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

The ADA2 c.506G>A variant is predicted to result in the amino acid substitution p.Arg169Gln. This variant in the compound heterozygous or homozygous state has been reported in patients with a complex immunologic and vascular phenotype, including polyarteritis nodosa (Navon Elkan et al. 2014. PubMed ID: 24552285; Van Eyck et al. 2015. PubMed ID: 25457153; Van Montfrans et al. 2016. PubMed ID: 26867732). This variant is reported in 0.19% of alleles in individuals of European (Finnish) descent in gnomAD. This variant is interpreted as pathogenic. -

Sneddon syndrome

Pathogenic:1

Jan 03, 2022

3billion

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000120303, PMID:24552285, PS1_S). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.87, 3CNET: 0.971, PP3_P). A missense variant is a common mechanism associated with Sneddon syndrome (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000474, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Pathogenic

0.16

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T;T;T;T;.;.

Eigen

Benign

0.19

Eigen_PC

Benign

-0.074

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.89

D;.;.;.;D;.;D

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.27

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.57

PhyloP100

3.9

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.7

.;D;D;D;.;D;.

REVEL

Pathogenic

0.87

Sift

Pathogenic

0.0

.;D;D;D;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;.;D;.

Polyphen

1.0

.;D;D;D;D;.;.

Vest4

0.75

MVP

0.93

MPC

0.33

ClinPred

0.12

GERP RS

2.2

Varity_R

0.86

gMVP

0.76

Mutation Taster

=8/92

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over