rs2839672

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_001134366.2(GAD2):c.458C>A(p.Pro153Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,613,700 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 39 hom. )

Consequence

GAD2
NM_001134366.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.57

Publications

8 publications found

Variant links:

Genes affected

GAD2 (HGNC:4093): (glutamate decarboxylase 2) This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for this enzyme has been identified in the human pancreas since it has been identified as an autoantibody and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2008]

GAD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.009708941).

BP6

Variant 10-26219214-C-A is Benign according to our data. Variant chr10-26219214-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 782118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 793 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_001134366.2 link	c.458C>A	p.Pro153Gln	missense_variant	Exon 4 of 16	ENST00000376261.8	NP_001127838.1	Q05329Q5VZ30
GAD2	NM_000818.3 link	c.458C>A	p.Pro153Gln	missense_variant	Exon 4 of 17		NP_000809.1	Q05329Q5VZ30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAD2	ENST00000376261.8 link	c.458C>A	p.Pro153Gln	missense_variant	Exon 4 of 16	1	NM_001134366.2	ENSP00000365437.3		Q05329

Frequencies

GnomAD3 genomes

AF:

0.00521

AC:

793

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00801

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00551

AC:

1384

AN:

251140

AF XY:

0.00559

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00835

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00673

AC:

9840

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

4851

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.000926

AC:

AN:

33478

American (AMR)

AF:

0.00148

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00352

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39662

South Asian (SAS)

AF:

0.00326

AC:

281

AN:

86134

European-Finnish (FIN)

AF:

0.00983

AC:

525

AN:

53414

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00763

AC:

8478

AN:

1111796

Other (OTH)

AF:

0.00586

AC:

354

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

486

972

1457

1943

2429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00521

AC:

793

AN:

152268

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41552

American (AMR)

AF:

0.00203

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.00373

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0108

AC:

115

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00801

AC:

545

AN:

68008

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00449

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00607

AC:

737

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00720

EpiControl

AF:

0.00741

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GAD2: BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

D;D;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D

MetaRNN

Benign

0.0097

T;T;T

MetaSVM

Benign

-0.28

MutationAssessor

Pathogenic

3.0

M;M;.

PhyloP100

7.6

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.6

D;D;.

REVEL

Uncertain

0.45

Sift

Uncertain

0.014

D;D;.

Sift4G

Uncertain

0.019

D;D;.

Polyphen

0.99

D;D;.

Vest4

0.80

MVP

0.59

MPC

1.2

ClinPred

0.017

GERP RS

5.6

Varity_R

0.78

gMVP

0.89

Mutation Taster

=35/65

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs2839672

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