rs2839673

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001134366.2(GAD2):c.695G>A(p.Gly232Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00782 in 1,613,388 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 69 hom. )

Consequence

GAD2
NM_001134366.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.27

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071927905).

BP6

Variant 10-26224622-G-A is Benign according to our data. Variant chr10-26224622-G-A is described in ClinVar as [Benign]. Clinvar id is 774469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_001134366.2 link	c.695G>A	p.Gly232Glu	missense_variant	Exon 6 of 16	ENST00000376261.8	NP_001127838.1	Q05329Q5VZ30
GAD2	NM_000818.3 link	c.695G>A	p.Gly232Glu	missense_variant	Exon 6 of 17		NP_000809.1	Q05329Q5VZ30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GAD2	ENST00000376261.8 link	c.695G>A	p.Gly232Glu	missense_variant	Exon 6 of 16	1	NM_001134366.2	ENSP00000365437.3	Q05329
GAD2	ENST00000259271.7 link	c.695G>A	p.Gly232Glu	missense_variant	Exon 6 of 17	1		ENSP00000259271.3	Q05329
GAD2	ENST00000648567.1 link	c.353G>A	p.Gly118Glu	missense_variant	Exon 6 of 17			ENSP00000498009.1	A0A3B3IU09
GAD2	ENST00000376248.1 link	n.542G>A		non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

898

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00961

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00875

Gnomad OTH

AF:

0.00814

GnomAD2 exomes

AF:

0.00646

AC:

1621

AN:

251122

AF XY:

0.00626

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00994

Gnomad NFE exome

AF:

0.00913

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00802

AC:

11719

AN:

1461122

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

5663

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

33476

American (AMR)

AF:

0.00291

AC:

130

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

369

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00252

AC:

217

AN:

86208

European-Finnish (FIN)

AF:

0.00927

AC:

495

AN:

53416

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00895

AC:

9951

AN:

1111400

Other (OTH)

AF:

0.00818

AC:

494

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

512

1024

1537

2049

2561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00590

AC:

898

AN:

152266

Hom.:

Cov.:

AF XY:

0.00602

AC XY:

448

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41548

American (AMR)

AF:

0.00425

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00249

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00961

AC:

102

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00875

AC:

595

AN:

68024

Other (OTH)

AF:

0.00806

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00781

Hom.:

Bravo

AF:

0.00557

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00674

AC:

818

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00688

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.24

T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

.;D;D

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

N;N;.

PhyloP100

6.3

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.29

N;N;.

REVEL

Benign

0.073

Sift

Benign

0.47

T;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.046

B;B;.

Vest4

0.28

MVP

0.10

MPC

0.52

ClinPred

0.025

GERP RS

5.2

Varity_R

0.32

gMVP

0.88

Mutation Taster

=78/22

polymorphism

(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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rs2839673

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