Genetic Variant GAD2:c.724+632A>C (chr10-26225283-A-C) – 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.724+632A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,148 control chromosomes in the GnomAD database, including 7,040 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 ( 7040 hom., cov: 32)

Consequence

GAD2
NM_001134366.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134366.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD2	NM_001134366.2	MANE Select	c.724+632A>C		intron	N/A	NP_001127838.1	Q5VZ30
	GAD2	NM_000818.3		c.724+632A>C		intron	N/A	NP_000809.1	Q05329

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GAD2	ENST00000376261.8	TSL:1 MANE Select	c.724+632A>C	intron	N/A	ENSP00000365437.3	Q05329
GAD2	ENST00000259271.7	TSL:1	c.724+632A>C	intron	N/A	ENSP00000259271.3	Q05329
GAD2	ENST00000648567.1		c.382+632A>C	intron	N/A	ENSP00000498009.1	A0A3B3IU09

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33134

AN:

152030

Hom.:

7010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0989

Gnomad EAS

AF:

0.0483

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0882

Gnomad OTH

AF:

0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.218

AC:

33215

AN:

152148

Hom.:

7040

Cov.:

AF XY:

0.213

AC XY:

15839

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.558

AC:

23113

AN:

41446

American (AMR)

AF:

0.143

AC:

2184

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0989

AC:

343

AN:

3468

East Asian (EAS)

AF:

0.0480

AC:

249

AN:

5188

South Asian (SAS)

AF:

0.0284

AC:

137

AN:

4822

European-Finnish (FIN)

AF:

0.0706

AC:

749

AN:

10614

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0882

AC:

5996

AN:

68010

Other (OTH)

AF:

0.184

AC:

388

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

973

1947

2920

3894

4867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.148

Hom.:

963

Bravo

AF:

0.243

Asia WGS

AF:

0.0880

AC:

308

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.57

PhyloP100

-1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over