rs7072137

Variant names:

• chr10-26268038-A-G
• rs7072137
• NM_001134366.2:c.921-1081A>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.921-1081A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,214 control chromosomes in the GnomAD database, including 2,707 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 0.16 (2707 hom., cov: 32)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAD2	NM_001134366.2	c.921-1081A>G		intron_variant	Intron 8 of 15	ENST00000376261.8	NP_001127838.1
GAD2	NM_000818.3	c.921-1081A>G		intron_variant	Intron 8 of 16		NP_000809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAD2	ENST00000376261.8	c.921-1081A>G		intron_variant	Intron 8 of 15	1	NM_001134366.2	ENSP00000365437.3
GAD2	ENST00000259271.7	c.921-1081A>G		intron_variant	Intron 8 of 16	1		ENSP00000259271.3
GAD2	ENST00000648567.1	c.579-1081A>G		intron_variant	Intron 8 of 16			ENSP00000498009.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23956 AN: 152096 Hom.: 2701 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.158 AC: 23986 AN: 152214 Hom.: 2707 Cov.: 32 AF XY: 0.153 AC XY: 11420 AN XY: 74414

African (AFR) AF: 0.325 AC: 13479 AN: 41502

American (AMR) AF: 0.116 AC: 1774 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.0514 AC: 267 AN: 5190

South Asian (SAS) AF: 0.0232 AC: 112 AN: 4822

European-Finnish (FIN) AF: 0.0772 AC: 819 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0999 AC: 6796 AN: 68020

Other (OTH) AF: 0.136 AC: 288 AN: 2110

Alfa AF: 0.143 Hom.: 364

Bravo AF: 0.172

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.051
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: rs7072137; hg19: chr10-26556967;