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GeneBe

10-26224632-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001134366.2(GAD2):c.705C>T(p.Gly235=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,611,374 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 24 hom. )

Consequence

GAD2
NM_001134366.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-26224632-C-T is Benign according to our data. Variant chr10-26224632-C-T is described in ClinVar as [Benign]. Clinvar id is 713603.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.43 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 512 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GAD2NM_001134366.2 linkuse as main transcriptc.705C>T p.Gly235= synonymous_variant 6/16 ENST00000376261.8
GAD2NM_000818.3 linkuse as main transcriptc.705C>T p.Gly235= synonymous_variant 6/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GAD2ENST00000376261.8 linkuse as main transcriptc.705C>T p.Gly235= synonymous_variant 6/161 NM_001134366.2 P1
GAD2ENST00000259271.7 linkuse as main transcriptc.705C>T p.Gly235= synonymous_variant 6/171 P1
GAD2ENST00000648567.1 linkuse as main transcriptc.363C>T p.Gly121= synonymous_variant 6/17
GAD2ENST00000376248.1 linkuse as main transcriptn.552C>T non_coding_transcript_exon_variant 4/45

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00337
AC:
512
AN:
152148
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000821
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.00177
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00373
Gnomad FIN
AF:
0.00387
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00560
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00382
AC:
958
AN:
250914
Hom.:
4
AF XY:
0.00406
AC XY:
550
AN XY:
135622
show subpopulations
Gnomad AFR exome
AF:
0.000985
Gnomad AMR exome
AF:
0.00215
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00538
Gnomad FIN exome
AF:
0.00351
Gnomad NFE exome
AF:
0.00522
Gnomad OTH exome
AF:
0.00572
GnomAD4 exome
AF:
0.00438
AC:
6384
AN:
1459108
Hom.:
24
Cov.:
29
AF XY:
0.00446
AC XY:
3235
AN XY:
726032
show subpopulations
Gnomad4 AFR exome
AF:
0.000598
Gnomad4 AMR exome
AF:
0.00242
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00547
Gnomad4 FIN exome
AF:
0.00397
Gnomad4 NFE exome
AF:
0.00481
Gnomad4 OTH exome
AF:
0.00372
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00337
AC:
513
AN:
152266
Hom.:
5
Cov.:
32
AF XY:
0.00328
AC XY:
244
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.000818
Gnomad4 AMR
AF:
0.00176
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00394
Gnomad4 FIN
AF:
0.00387
Gnomad4 NFE
AF:
0.00560
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00457
Hom.:
2
Bravo
AF:
0.00284
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.00463
EpiControl
AF:
0.00391

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
1.4
Dann
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs55789936; hg19: chr10-26513561; COSMIC: COSV104581754; API