rs12243037

Variant names:

• chr10-26235445-G-A
• rs12243037
• NM_001134366.2:c.840+5668G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-26235445-G-A
• chr10-26235445-G-C

Variant summary

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

The NM_001134366.2(GAD2):​c.840+5668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,124 control chromosomes in the GnomAD database, including 2,807 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 0.19 (2807 hom., cov: 32)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_001134366.2	c.840+5668G>A		intron_variant	Intron 7 of 15	ENST00000376261.8	NP_001127838.1
GAD2	NM_000818.3	c.840+5668G>A		intron_variant	Intron 7 of 16		NP_000809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAD2	ENST00000376261.8	c.840+5668G>A		intron_variant	Intron 7 of 15	1	NM_001134366.2	ENSP00000365437.3
GAD2	ENST00000259271.7	c.840+5668G>A		intron_variant	Intron 7 of 16	1		ENSP00000259271.3
GAD2	ENST00000648567.1	c.498+5668G>A		intron_variant	Intron 7 of 16			ENSP00000498009.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28593 AN: 152008 Hom.: 2805 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.188 AC: 28606 AN: 152124 Hom.: 2807 Cov.: 32 AF XY: 0.190 AC XY: 14104 AN XY: 74356

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.207

Alfa AF: 0.172 Hom.: 622

Bravo AF: 0.193

Asia WGS AF: 0.258 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.48

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: rs12243037; hg19: chr10-26524374;