NM_001134366.2:c.724+632A>C

Variant names:

• chr10-26225283-A-C
• rs7908975
• NM_001134366.2:c.724+632A>C

Variant summary

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

The NM_001134366.2(GAD2):​c.724+632A>C 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 152,148 control chromosomes in the GnomAD database, including 7,040 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 (7040 hom., cov: 32)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134366.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD2	NM_001134366.2	MANE Select	c.724+632A>C		intron	N/A	NP_001127838.1	Q5VZ30
	GAD2	NM_000818.3		c.724+632A>C		intron	N/A	NP_000809.1	Q05329

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD2	ENST00000376261.8	TSL:1 MANE Select	c.724+632A>C		intron	N/A	ENSP00000365437.3	Q05329
	GAD2	ENST00000259271.7	TSL:1	c.724+632A>C		intron	N/A	ENSP00000259271.3	Q05329
	GAD2	ENST00000648567.1		c.382+632A>C		intron	N/A	ENSP00000498009.1	A0A3B3IU09

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33134 AN: 152030 Hom.: 7010 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0989

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.218 AC: 33215 AN: 152148 Hom.: 7040 Cov.: 32 AF XY: 0.213 AC XY: 15839 AN XY: 74378

African (AFR) AF: 0.558 AC: 23113 AN: 41446

American (AMR) AF: 0.143 AC: 2184 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0989 AC: 343 AN: 3468

East Asian (EAS) AF: 0.0480 AC: 249 AN: 5188

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4822

European-Finnish (FIN) AF: 0.0706 AC: 749 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0882 AC: 5996 AN: 68010

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.148 Hom.: 963

Bravo AF: 0.243

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-1.5
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: rs7908975; hg19: chr10-26514212;