rs8190612

Positions:

• chr10-26223446-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134366.2(GAD2):​c.521-441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 152,062 control chromosomes in the GnomAD database, including 913 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 0.095 (913 hom., cov: 32)
• Consequence: GAD2 NM_001134366.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAD2	NM_001134366.2	c.521-441C>T		intron_variant		ENST00000376261.8	NP_001127838.1
GAD2	NM_000818.3	c.521-441C>T		intron_variant			NP_000809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAD2	ENST00000376261.8	c.521-441C>T		intron_variant		1	NM_001134366.2	ENSP00000365437	P1
GAD2	ENST00000259271.7	c.521-441C>T		intron_variant		1		ENSP00000259271	P1
GAD2	ENST00000648567.1	c.179-441C>T		intron_variant				ENSP00000498009
GAD2	ENST00000376248.1	n.368-441C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14528 AN: 151944 Hom.: 914 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0955 AC: 14517 AN: 152062 Hom.: 913 Cov.: 32 AF XY: 0.0959 AC XY: 7128 AN XY: 74322

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0309

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.104

Alfa AF: 0.125 Hom.: 1641

Bravo AF: 0.0808

Asia WGS AF: 0.0630 AC: 219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs8190612; hg19: chr10-26512375;