rs8190598

chr10-26218666-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134366.2(GAD2):c.287-377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,962 control chromosomes in the GnomAD database, including 3,190 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 0.20 (3190 hom., cov: 32)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAD2	NM_001134366.2	c.287-377A>G		intron_variant		ENST00000376261.8
GAD2	NM_000818.3	c.287-377A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAD2	ENST00000376261.8	c.287-377A>G		intron_variant		1	NM_001134366.2	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30127 AN: 151844 Hom.: 3187 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.198 AC: 30146 AN: 151962 Hom.: 3190 Cov.: 32 AF XY: 0.200 AC XY: 14836 AN XY: 74276

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.217

Alfa AF: 0.177 Hom.: 299

Bravo AF: 0.206

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.0
Dann	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs8190598; hg19: chr10-26507595;