Variant 10-26224632-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

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]

GAD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BS2

High AC in GnomAd4 at 513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAD2	NM_001134366.2 linkuse as main transcript	c.705C>T	p.Gly235=	synonymous_variant	6/16	ENST00000376261.8
GAD2	NM_000818.3 linkuse as main transcript	c.705C>T	p.Gly235=	synonymous_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GAD2	ENST00000376261.8 linkuse as main transcript	c.705C>T	p.Gly235=	synonymous_variant	6/16	1	NM_001134366.2	P1
GAD2	ENST00000259271.7 linkuse as main transcript	c.705C>T	p.Gly235=	synonymous_variant	6/17	1		P1
GAD2	ENST00000648567.1 linkuse as main transcript	c.363C>T	p.Gly121=	synonymous_variant	6/17
GAD2	ENST00000376248.1 linkuse as main transcript	n.552C>T		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

512

AN:

152148

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00337

AC:

513

AN:

152266

Hom.:

Cov.:

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.:

Bravo

AF:

0.00284

Asia WGS

AF:

0.00231

AC:

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 submitter

clinical testing

Invitae

May 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over