Variant 10-26229742-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001134366.2(GAD2):c.805G>A(p.Ala269Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00486 in 1,613,924 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 27 hom. )

Consequence

GAD2
NM_001134366.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006244868).

BP6

Variant 10-26229742-G-A is Benign according to our data. Variant chr10-26229742-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 713281.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 492 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAD2	NM_001134366.2 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	7/16	ENST00000376261.8
GAD2	NM_000818.3 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	7/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GAD2	ENST00000376261.8 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	7/16	1	NM_001134366.2	P1
GAD2	ENST00000259271.7 linkuse as main transcript	c.805G>A	p.Ala269Thr	missense_variant	7/17	1		P1
GAD2	ENST00000648567.1 linkuse as main transcript	c.463G>A	p.Ala155Thr	missense_variant	7/17

Frequencies

GnomAD3 genomes

AF:

0.00324

AC:

493

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00566

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00277

AC:

697

AN:

251388

Hom.:

AF XY:

0.00275

AC XY:

373

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00277

Gnomad NFE exome

AF:

0.00491

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00503

AC:

7359

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

3536

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00230

Gnomad4 NFE exome

AF:

0.00621

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00323

AC:

492

AN:

152332

Hom.:

Cov.:

AF XY:

0.00315

AC XY:

235

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.00564

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00432

Hom.:

Bravo

AF:

0.00305

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00300

AC:

364

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00492

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.0097

MetaRNN

Benign

0.0062

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.096

T;T;.

Sift4G

Benign

0.16

T;T;.

Polyphen

0.12

B;B;.

Vest4

0.41

MVP

0.47

MPC

0.45

ClinPred

0.028

GERP RS

5.6

Varity_R

0.30

gMVP

0.83

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.

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