Variant chr10-26270630-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001134366.2(GAD2):c.976-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,598,540 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 14 hom. )

Consequence

GAD2
NM_001134366.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001562

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31

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 -16 ACMG points.

BP4

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

BP6

Variant 10-26270630-G-A is Benign according to our data. Variant chr10-26270630-G-A is described in ClinVar as [Benign]. Clinvar id is 788279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAD2	NM_001134366.2 linkuse as main transcript	c.976-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000376261.8
GAD2	NM_000818.3 linkuse as main transcript	c.976-10G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
GAD2	ENST00000376261.8 linkuse as main transcript	c.976-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001134366.2	P1
GAD2	ENST00000259271.7 linkuse as main transcript	c.976-10G>A	splice_polypyrimidine_tract_variant, intron_variant	1		P1
GAD2	ENST00000648567.1 linkuse as main transcript	c.634-10G>A	splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00219

AC:

550

AN:

250808

Hom.:

AF XY:

0.00227

AC XY:

308

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.00585

Gnomad AMR exome

AF:

0.00273

Gnomad ASJ exome

AF:

0.00696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00469

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000987

Gnomad OTH exome

AF:

0.00588

GnomAD4 exome

AF:

0.00112

AC:

1627

AN:

1446284

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

938

AN XY:

720530

show subpopulations

Gnomad4 AFR exome

AF:

0.00488

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.00707

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00414

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000516

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152256

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00541

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00333

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000970

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00297

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Aug 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0020

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.038

SpliceAI score (max)

0.010

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