Variant chr10-26245880-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134366.2(GAD2):c.841-41G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,457,100 control chromosomes in the GnomAD database, including 9,634 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 0.16 ( 2840 hom., cov: 32)

Exomes 𝑓: 0.091 ( 6794 hom. )

Consequence

GAD2
NM_001134366.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAD2	NM_001134366.2 linkuse as main transcript	c.841-41G>T		intron_variant		ENST00000376261.8	NP_001127838.1	Q05329Q5VZ30
GAD2	NM_000818.3 linkuse as main transcript	c.841-41G>T		intron_variant			NP_000809.1	Q05329Q5VZ30

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GAD2	ENST00000376261.8 linkuse as main transcript	c.841-41G>T	intron_variant	1	NM_001134366.2	ENSP00000365437.3	Q05329
GAD2	ENST00000259271.7 linkuse as main transcript	c.841-41G>T	intron_variant	1		ENSP00000259271.3	Q05329
GAD2	ENST00000648567.1 linkuse as main transcript	c.499-41G>T	intron_variant			ENSP00000498009.1	A0A3B3IU09

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23933

AN:

152088

Hom.:

2822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0918

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.0904

AC:

21298

AN:

235622

Hom.:

1474

AF XY:

0.0849

AC XY:

10882

AN XY:

128232

show subpopulations

Gnomad AFR exome

AF:

0.336

Gnomad AMR exome

AF:

0.0660

Gnomad ASJ exome

AF:

0.0934

Gnomad EAS exome

AF:

0.0548

Gnomad SAS exome

AF:

0.0248

Gnomad FIN exome

AF:

0.0769

Gnomad NFE exome

AF:

0.0911

Gnomad OTH exome

AF:

0.0876

GnomAD4 exome

AF:

0.0911

AC:

118937

AN:

1304894

Hom.:

6794

Cov.:

AF XY:

0.0885

AC XY:

58178

AN XY:

657250

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.0719

Gnomad4 ASJ exome

AF:

0.0940

Gnomad4 EAS exome

AF:

0.0448

Gnomad4 SAS exome

AF:

0.0262

Gnomad4 FIN exome

AF:

0.0805

Gnomad4 NFE exome

AF:

0.0917

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.158

AC:

23990

AN:

152206

Hom.:

2840

Cov.:

AF XY:

0.155

AC XY:

11498

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.338

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.0501

Gnomad4 SAS

AF:

0.0249

Gnomad4 FIN

AF:

0.0767

Gnomad4 NFE

AF:

0.0917

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.0948

Hom.:

828

Bravo

AF:

0.171

Asia WGS

AF:

0.0670

AC:

234

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.0

DANN

Benign

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over