rs7076544

Variant summary

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

The NM_001134366.2(GAD2):​c.921-323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,156 control chromosomes in the GnomAD database, including 12,027 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 0.33 ( 12027 hom., cov: 33)

Consequence

GAD2
NM_001134366.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0620
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAD2NM_001134366.2 linkc.921-323A>G intron_variant Intron 8 of 15 ENST00000376261.8 NP_001127838.1 Q05329Q5VZ30
GAD2NM_000818.3 linkc.921-323A>G intron_variant Intron 8 of 16 NP_000809.1 Q05329Q5VZ30

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAD2ENST00000376261.8 linkc.921-323A>G intron_variant Intron 8 of 15 1 NM_001134366.2 ENSP00000365437.3 Q05329
GAD2ENST00000259271.7 linkc.921-323A>G intron_variant Intron 8 of 16 1 ENSP00000259271.3 Q05329
GAD2ENST00000648567.1 linkc.579-323A>G intron_variant Intron 8 of 16 ENSP00000498009.1 A0A3B3IU09

Frequencies

GnomAD3 genomes
AF:
0.330
AC:
50172
AN:
152038
Hom.:
11993
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.678
Gnomad AMI
AF:
0.247
Gnomad AMR
AF:
0.251
Gnomad ASJ
AF:
0.180
Gnomad EAS
AF:
0.307
Gnomad SAS
AF:
0.259
Gnomad FIN
AF:
0.141
Gnomad MID
AF:
0.307
Gnomad NFE
AF:
0.182
Gnomad OTH
AF:
0.311
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.330
AC:
50249
AN:
152156
Hom.:
12027
Cov.:
33
AF XY:
0.327
AC XY:
24294
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.678
Gnomad4 AMR
AF:
0.251
Gnomad4 ASJ
AF:
0.180
Gnomad4 EAS
AF:
0.307
Gnomad4 SAS
AF:
0.258
Gnomad4 FIN
AF:
0.141
Gnomad4 NFE
AF:
0.182
Gnomad4 OTH
AF:
0.311
Alfa
AF:
0.260
Hom.:
948
Bravo
AF:
0.353
Asia WGS
AF:
0.298
AC:
1036
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
1.7
DANN
Benign
0.54

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

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

Other links and lift over

dbSNP: rs7076544; hg19: chr10-26557725; API