rs2368160

Variant names:

• chr10-26251842-G-A
• rs2368160
• NM_001134366.2:c.920+5842G>A

Variant summary

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

The NM_000818.3(GAD2):​c.920+5842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,088 control chromosomes in the GnomAD database, including 14,691 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 0.40 (14691 hom., cov: 32)
• Consequence: GAD2 NM_000818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD2	NM_001134366.2	MANE Select	c.920+5842G>A		intron	N/A	NP_001127838.1
	GAD2	NM_000818.3		c.920+5842G>A		intron	N/A	NP_000809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD2	ENST00000376261.8	TSL:1 MANE Select	c.920+5842G>A		intron	N/A	ENSP00000365437.3
	GAD2	ENST00000259271.7	TSL:1	c.920+5842G>A		intron	N/A	ENSP00000259271.3
	GAD2	ENST00000648567.1		c.578+5842G>A		intron	N/A	ENSP00000498009.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60436 AN: 151970 Hom.: 14658 Cov.: 32

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.398 AC: 60516 AN: 152088 Hom.: 14691 Cov.: 32 AF XY: 0.394 AC XY: 29267 AN XY: 74346

African (AFR) AF: 0.693 AC: 28759 AN: 41472

American (AMR) AF: 0.328 AC: 5013 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3466

East Asian (EAS) AF: 0.356 AC: 1840 AN: 5170

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4822

European-Finnish (FIN) AF: 0.218 AC: 2310 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19064 AN: 67976

Other (OTH) AF: 0.384 AC: 811 AN: 2112

Alfa AF: 0.335 Hom.: 20364

Bravo AF: 0.421

Asia WGS AF: 0.345 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.053
DANN	Benign	0.16
PhyloP100		-1.8
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: rs2368160; hg19: chr10-26540771;