dbSNP rs2236418: GAD2:c.-243A>G (chr10-26216567-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000818.3(GAD2):c.-243A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 369,476 control chromosomes in the GnomAD database, including 20,826 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 14906 hom., cov: 32)

Exomes 𝑓: 0.20 ( 5920 hom. )

Consequence

GAD2
NM_000818.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.638

Publications

29 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_000818.3 link	c.-243A>G		5_prime_UTR_variant	Exon 1 of 17		NP_000809.1	Q05329Q5VZ30
GAD2	NM_001134366.2 link	c.-243A>G		upstream_gene_variant		ENST00000376261.8	NP_001127838.1	Q05329Q5VZ30

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GAD2	ENST00000376261.8 link	c.-243A>G	upstream_gene_variant	1	NM_001134366.2	ENSP00000365437.3	Q05329
GAD2	ENST00000259271.7 link	c.-243A>G	upstream_gene_variant	1		ENSP00000259271.3	Q05329
GAD2	ENST00000428517.2 link	n.-243A>G	upstream_gene_variant	1		ENSP00000390434.2	Q5VZ31

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53967

AN:

151854

Hom.:

14858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.204

AC:

44455

AN:

217504

Hom.:

5920

Cov.:

AF XY:

0.204

AC XY:

23083

AN XY:

113028

show subpopulations

African (AFR)

AF:

0.769

AC:

3615

AN:

4702

American (AMR)

AF:

0.261

AC:

1175

AN:

4494

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

1123

AN:

6868

East Asian (EAS)

AF:

0.392

AC:

5459

AN:

13942

South Asian (SAS)

AF:

0.228

AC:

3075

AN:

13514

European-Finnish (FIN)

AF:

0.132

AC:

2386

AN:

18118

Middle Eastern (MID)

AF:

0.292

AC:

305

AN:

1046

European-Non Finnish (NFE)

AF:

0.171

AC:

24195

AN:

141194

Other (OTH)

AF:

0.229

AC:

3122

AN:

13626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1526

3051

4577

6102

7628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.356

AC:

54073

AN:

151972

Hom.:

14906

Cov.:

AF XY:

0.353

AC XY:

26224

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.774

AC:

32091

AN:

41474

American (AMR)

AF:

0.278

AC:

4246

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

580

AN:

3468

East Asian (EAS)

AF:

0.319

AC:

1643

AN:

5156

South Asian (SAS)

AF:

0.239

AC:

1146

AN:

4802

European-Finnish (FIN)

AF:

0.133

AC:

1406

AN:

10556

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11954

AN:

67936

Other (OTH)

AF:

0.334

AC:

705

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1282

2564

3846

5128

6410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.242

Hom.:

26192

Bravo

AF:

0.387

Asia WGS

AF:

0.307

AC:

1069

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.47

PhyloP100

-0.64

PromoterAI

-0.0037

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over