rs8190748

Positions:

• chr10-26280826-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.1158-183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,906 control chromosomes in the GnomAD database, including 17,851 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 0.43 (17851 hom., cov: 31)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAD2	NM_001134366.2	c.1158-183A>G		intron_variant		ENST00000376261.8	NP_001127838.1
GAD2	NM_000818.3	c.1158-183A>G		intron_variant			NP_000809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAD2	ENST00000376261.8	c.1158-183A>G		intron_variant		1	NM_001134366.2	ENSP00000365437	P1
GAD2	ENST00000259271.7	c.1158-183A>G		intron_variant		1		ENSP00000259271	P1
GAD2	ENST00000648567.1	c.816-183A>G		intron_variant				ENSP00000498009

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64839 AN: 151788 Hom.: 17805 Cov.: 31

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.427 AC: 64937 AN: 151906 Hom.: 17851 Cov.: 31 AF XY: 0.423 AC XY: 31413 AN XY: 74262

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.406

Alfa AF: 0.358 Hom.: 1898

Bravo AF: 0.455

Asia WGS AF: 0.347 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.17

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

Other links and lift over

dbSNP: rs8190748; hg19: chr10-26569755;