rs6482538

Variant names:

• chr10-26220935-A-G
• rs6482538
• NM_001134366.2:c.520+1659A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134366.2(GAD2):​c.520+1659A>G 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 152,184 control chromosomes in the GnomAD database, including 7,011 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 (7011 hom., cov: 33)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_001134366.2	c.520+1659A>G		intron_variant	Intron 4 of 15	ENST00000376261.8	NP_001127838.1
GAD2	NM_000818.3	c.520+1659A>G		intron_variant	Intron 4 of 16		NP_000809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAD2	ENST00000376261.8	c.520+1659A>G		intron_variant	Intron 4 of 15	1	NM_001134366.2	ENSP00000365437.3
GAD2	ENST00000259271.7	c.520+1659A>G		intron_variant	Intron 4 of 16	1		ENSP00000259271.3
GAD2	ENST00000648567.1	c.178+1659A>G		intron_variant	Intron 4 of 16			ENSP00000498009.1
GAD2	ENST00000376248.1	n.367+1659A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33096 AN: 152066 Hom.: 6981 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0703

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.218 AC: 33178 AN: 152184 Hom.: 7011 Cov.: 33 AF XY: 0.213 AC XY: 15849 AN XY: 74422

African (AFR) AF: 0.556 AC: 23057 AN: 41438

American (AMR) AF: 0.143 AC: 2188 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3470

East Asian (EAS) AF: 0.0507 AC: 263 AN: 5190

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4826

European-Finnish (FIN) AF: 0.0703 AC: 747 AN: 10620

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0881 AC: 5993 AN: 68022

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.147 Hom.: 1202

Bravo AF: 0.243

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.65
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6482538; hg19: chr10-26509864;