NM_001134366.2:c.1585-92T>A

Variant names:

• chr10-26300696-T-A
• rs928197
• NM_001134366.2:c.1585-92T>A

Variant summary

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

The NM_001134366.2(GAD2):​c.1585-92T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,204,716 control chromosomes in the GnomAD database, including 25,604 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 (4193 hom., cov: 32)
  • Exomes 𝑓: 0.20 (21411 hom.)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908
• 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]

ENSG00000289350 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD2	NM_001134366.2	MANE Select	c.1585-92T>A		intron	N/A	NP_001127838.1
	GAD2	NM_000818.3		c.1585-92T>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.1585-92T>A		intron	N/A	ENSP00000365437.3
	GAD2	ENST00000259271.7	TSL:1	c.1585-92T>A		intron	N/A	ENSP00000259271.3
	GAD2	ENST00000648567.1		c.1243-92T>A		intron	N/A	ENSP00000498009.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34154 AN: 152004 Hom.: 4191 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.197 AC: 207684 AN: 1052594 Hom.: 21411 AF XY: 0.198 AC XY: 105535 AN XY: 532596

African (AFR) AF: 0.325 AC: 7902 AN: 24328

American (AMR) AF: 0.185 AC: 5816 AN: 31496

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 3242 AN: 19270

East Asian (EAS) AF: 0.319 AC: 11980 AN: 37592

South Asian (SAS) AF: 0.242 AC: 16022 AN: 66184

European-Finnish (FIN) AF: 0.147 AC: 6913 AN: 46922

Middle Eastern (MID) AF: 0.263 AC: 875 AN: 3328

European-Non Finnish (NFE) AF: 0.187 AC: 145720 AN: 777428

Other (OTH) AF: 0.200 AC: 9214 AN: 46046

GnomAD4 genome AF: 0.225 AC: 34172 AN: 152122 Hom.: 4193 Cov.: 32 AF XY: 0.225 AC XY: 16734 AN XY: 74376

African (AFR) AF: 0.316 AC: 13095 AN: 41484

American (AMR) AF: 0.204 AC: 3120 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1579 AN: 5172

South Asian (SAS) AF: 0.249 AC: 1197 AN: 4808

European-Finnish (FIN) AF: 0.144 AC: 1525 AN: 10596

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12266 AN: 67988

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.198 Hom.: 382

Bravo AF: 0.232

Asia WGS AF: 0.260 AC: 906 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.7
DANN	Benign	0.83
PhyloP100		0.91
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: rs928197; hg19: chr10-26589625; COSMIC: COSV52150878;