Variant rs2839677 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134366.2(GAD2):c.920+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 1,611,080 control chromosomes in the GnomAD database, including 5,916 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 401 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5515 hom. )

Consequence

GAD2
NM_001134366.2 splice_region, intron

Scores

Splicing: ADA: 0.00002904

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Variant links:

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]

GAD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAD2	NM_001134366.2 linkuse as main transcript	c.920+8C>T		splice_region_variant, intron_variant		ENST00000376261.8	NP_001127838.1	Q05329Q5VZ30
GAD2	NM_000818.3 linkuse as main transcript	c.920+8C>T		splice_region_variant, intron_variant			NP_000809.1	Q05329Q5VZ30

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GAD2	ENST00000376261.8 linkuse as main transcript	c.920+8C>T	splice_region_variant, intron_variant	1	NM_001134366.2	ENSP00000365437.3	Q05329
GAD2	ENST00000259271.7 linkuse as main transcript	c.920+8C>T	splice_region_variant, intron_variant	1		ENSP00000259271.3	Q05329
GAD2	ENST00000648567.1 linkuse as main transcript	c.578+8C>T	splice_region_variant, intron_variant			ENSP00000498009.1	A0A3B3IU09

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9871

AN:

152102

Hom.:

401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0760

Gnomad ASJ

AF:

0.0999

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.0251

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0905

Gnomad OTH

AF:

0.0718

GnomAD3 exomes

AF:

0.0688

AC:

17190

AN:

250012

Hom.:

703

AF XY:

0.0692

AC XY:

9349

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.0940

Gnomad EAS exome

AF:

0.0561

Gnomad SAS exome

AF:

0.0245

Gnomad FIN exome

AF:

0.0776

Gnomad NFE exome

AF:

0.0918

Gnomad OTH exome

AF:

0.0755

GnomAD4 exome

AF:

0.0830

AC:

121099

AN:

1458860

Hom.:

5515

Cov.:

AF XY:

0.0817

AC XY:

59308

AN XY:

725838

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.0514

Gnomad4 ASJ exome

AF:

0.0932

Gnomad4 EAS exome

AF:

0.0462

Gnomad4 SAS exome

AF:

0.0257

Gnomad4 FIN exome

AF:

0.0804

Gnomad4 NFE exome

AF:

0.0923

Gnomad4 OTH exome

AF:

0.0817

GnomAD4 genome

AF:

0.0648

AC:

9863

AN:

152220

Hom.:

401

Cov.:

AF XY:

0.0642

AC XY:

4781

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.0759

Gnomad4 ASJ

AF:

0.0999

Gnomad4 EAS

AF:

0.0501

Gnomad4 SAS

AF:

0.0249

Gnomad4 FIN

AF:

0.0767

Gnomad4 NFE

AF:

0.0904

Gnomad4 OTH

AF:

0.0710

Alfa

AF:

0.0808

Hom.:

241

Bravo

AF:

0.0652

Asia WGS

AF:

0.0440

AC:

155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.11

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over