chr10-26275504-T-G

Variant names:

• chr10-26275504-T-G
• rs7900976
• NM_001134366.2:c.1157+1804T>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.1157+1804T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,152 control chromosomes in the GnomAD database, including 4,974 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 0.24 (4974 hom., cov: 33)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_001134366.2	c.1157+1804T>G		intron_variant	Intron 11 of 15	ENST00000376261.8	NP_001127838.1
GAD2	NM_000818.3	c.1157+1804T>G		intron_variant	Intron 11 of 16		NP_000809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAD2	ENST00000376261.8	c.1157+1804T>G		intron_variant	Intron 11 of 15	1	NM_001134366.2	ENSP00000365437.3
GAD2	ENST00000259271.7	c.1157+1804T>G		intron_variant	Intron 11 of 16	1		ENSP00000259271.3
GAD2	ENST00000648567.1	c.815+1804T>G		intron_variant	Intron 11 of 16			ENSP00000498009.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36447 AN: 152034 Hom.: 4972 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.240 AC: 36471 AN: 152152 Hom.: 4974 Cov.: 33 AF XY: 0.239 AC XY: 17794 AN XY: 74392

African (AFR) AF: 0.367 AC: 15207 AN: 41476

American (AMR) AF: 0.210 AC: 3217 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 626 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1593 AN: 5172

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1490 AN: 10598

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12292 AN: 67990

Other (OTH) AF: 0.241 AC: 510 AN: 2114

Alfa AF: 0.205 Hom.: 4351

Bravo AF: 0.250

Asia WGS AF: 0.265 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.69
PhyloP100		-0.65
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: rs7900976; hg19: chr10-26564433;