dbSNP rs928197: GAD2:c.1585-92T>A (chr10-26300696-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001134366.2(GAD2):c.1585-92T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,204,716 control chromosomes in the GnomAD database, including 25,604 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 0.22 ( 4193 hom., cov: 32)

Exomes 𝑓: 0.20 ( 21411 hom. )

Consequence

GAD2
NM_001134366.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.908

Publications

4 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:

ENSG00000289350 (HGNC:):

ENSG00000289350 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_001134366.2 link	c.1585-92T>A		intron_variant	Intron 15 of 15	ENST00000376261.8	NP_001127838.1	Q05329Q5VZ30
GAD2	NM_000818.3 link	c.1585-92T>A		intron_variant	Intron 15 of 16		NP_000809.1	Q05329Q5VZ30

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GAD2	ENST00000376261.8 link	c.1585-92T>A	intron_variant	Intron 15 of 15	1	NM_001134366.2	ENSP00000365437.3	Q05329
GAD2	ENST00000259271.7 link	c.1585-92T>A	intron_variant	Intron 15 of 16	1		ENSP00000259271.3	Q05329
GAD2	ENST00000648567.1 link	c.1243-92T>A	intron_variant	Intron 15 of 16			ENSP00000498009.1	A0A3B3IU09
ENSG00000289350	ENST00000719940.1 link	n.119-7744A>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34154

AN:

152004

Hom.:

4191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.197

AC:

207684

AN:

1052594

Hom.:

21411

AF XY:

0.198

AC XY:

105535

AN XY:

532596

show subpopulations

African (AFR)

AF:

0.325

AC:

7902

AN:

24328

American (AMR)

AF:

0.185

AC:

5816

AN:

31496

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

3242

AN:

19270

East Asian (EAS)

AF:

0.319

AC:

11980

AN:

37592

South Asian (SAS)

AF:

0.242

AC:

16022

AN:

66184

European-Finnish (FIN)

AF:

0.147

AC:

6913

AN:

46922

Middle Eastern (MID)

AF:

0.263

AC:

875

AN:

3328

European-Non Finnish (NFE)

AF:

0.187

AC:

145720

AN:

777428

Other (OTH)

AF:

0.200

AC:

9214

AN:

46046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

8268

16536

24805

33073

41341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4800

9600

14400

19200

24000

<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:

0.225

AC:

34172

AN:

152122

Hom.:

4193

Cov.:

AF XY:

0.225

AC XY:

16734

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.316

AC:

13095

AN:

41484

American (AMR)

AF:

0.204

AC:

3120

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

602

AN:

3472

East Asian (EAS)

AF:

0.305

AC:

1579

AN:

5172

South Asian (SAS)

AF:

0.249

AC:

1197

AN:

4808

European-Finnish (FIN)

AF:

0.144

AC:

1525

AN:

10596

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12266

AN:

67988

Other (OTH)

AF:

0.229

AC:

483

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1345

2689

4034

5378

6723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.198

Hom.:

382

Bravo

AF:

0.232

Asia WGS

AF:

0.260

AC:

906

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.7

(source)

DANN

Benign

0.83

PhyloP100

0.91

Mutation Taster

=100/0

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