chr10-26217930-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_001134366.2(GAD2):c.225C>T(p.Cys75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,611,790 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0030 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 30 hom. )
Consequence
GAD2
NM_001134366.2 synonymous
NM_001134366.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.778
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 10-26217930-C-T is Benign according to our data. Variant chr10-26217930-C-T is described in ClinVar as [Benign]. Clinvar id is 771432.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.778 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00299 (455/152316) while in subpopulation AMR AF= 0.0198 (303/15310). AF 95% confidence interval is 0.018. There are 6 homozygotes in gnomad4. There are 239 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 452 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAD2 | NM_001134366.2 | c.225C>T | p.Cys75= | synonymous_variant | 3/16 | ENST00000376261.8 | |
GAD2 | NM_000818.3 | c.225C>T | p.Cys75= | synonymous_variant | 3/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAD2 | ENST00000376261.8 | c.225C>T | p.Cys75= | synonymous_variant | 3/16 | 1 | NM_001134366.2 | P1 | |
GAD2 | ENST00000259271.7 | c.225C>T | p.Cys75= | synonymous_variant | 3/17 | 1 | P1 | ||
GAD2 | ENST00000428517.2 | c.225C>T | p.Cys75= | synonymous_variant | 3/4 | 1 | |||
GAD2 | ENST00000648567.1 | c.-118C>T | 5_prime_UTR_variant | 3/17 |
Frequencies
GnomAD3 genomes ? AF: 0.00297 AC: 452AN: 152198Hom.: 6 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
452
AN:
152198
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00566 AC: 1382AN: 244332Hom.: 21 AF XY: 0.00432 AC XY: 576AN XY: 133320
GnomAD3 exomes
AF:
AC:
1382
AN:
244332
Hom.:
AF XY:
AC XY:
576
AN XY:
133320
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00156 AC: 2280AN: 1459474Hom.: 30 Cov.: 32 AF XY: 0.00146 AC XY: 1057AN XY: 725980
GnomAD4 exome
AF:
AC:
2280
AN:
1459474
Hom.:
Cov.:
32
AF XY:
AC XY:
1057
AN XY:
725980
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00299 AC: 455AN: 152316Hom.: 6 Cov.: 32 AF XY: 0.00321 AC XY: 239AN XY: 74478
GnomAD4 genome
?
AF:
AC:
455
AN:
152316
Hom.:
Cov.:
32
AF XY:
AC XY:
239
AN XY:
74478
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
11
AN:
3474
EpiCase
AF:
EpiControl
AF:
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 18, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at