2-170815865-C-T

Variant names:

• chr2-170815865-C-T
• rs6755102
• ENST00000454603.5:c.-64+2443C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454603.5(GAD1):​c.-64+2443C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 152,302 control chromosomes in the GnomAD database, including 235 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.021 (235 hom., cov: 33)
• Consequence: GAD1 ENST00000454603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 2 publications found

Genes affected

GAD1 (HGNC:4092): (glutamate decarboxylase 1) 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 autoantigen and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Deficiency in this enzyme has been shown to lead to pyridoxine dependency with seizures. Alternative splicing of this gene results in two products, the predominant 67-kD form and a less-frequent 25-kD form. [provided by RefSeq, Jul 2008]

ERICH2-DT (HGNC:55686): (ERICH2 divergent transcript)

GAD1-AS1 (HGNC:40250):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD1-AS1	NR_197761.1		n.1264G>A		non_coding_transcript_exon	Exon 4 of 4
	GAD1-AS1	NR_197762.1		n.1033G>A		non_coding_transcript_exon	Exon 3 of 3
	GAD1-AS1	NR_197763.1		n.1090G>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAD1	ENST00000454603.5	TSL:4	c.-64+2443C>T		intron	N/A	ENSP00000402366.1	C9JLZ7
	ERICH2-DT	ENST00000663207.2		n.959G>A		non_coding_transcript_exon	Exon 2 of 2
	ERICH2-DT	ENST00000728834.1		n.358+989G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3202 AN: 152184 Hom.: 236 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.0287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0211 AC: 3211 AN: 152302 Hom.: 235 Cov.: 33 AF XY: 0.0229 AC XY: 1707 AN XY: 74462

African (AFR) AF: 0.0184 AC: 767 AN: 41572

American (AMR) AF: 0.0197 AC: 301 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1406 AN: 5150

South Asian (SAS) AF: 0.0430 AC: 208 AN: 4832

European-Finnish (FIN) AF: 0.00509 AC: 54 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00550 AC: 374 AN: 68034

Other (OTH) AF: 0.0293 AC: 62 AN: 2116

Alfa AF: 0.00581 Hom.: 4

Bravo AF: 0.0230

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.4
DANN	Benign	0.82
PhyloP100		-0.97
PromoterAI		0.043	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6755102;

hg19: chr2-171672375;