rs2236418

Positions:

• chr10-26216567-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000818.3(GAD2):​c.-243A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 369,476 control chromosomes in the GnomAD database, including 20,826 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 0.36 (14906 hom., cov: 32)
  • Exomes 𝑓: 0.20 (5920 hom.)
• Consequence: GAD2 NM_000818.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

Genes affected

GAD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAD2	NM_000818.3	c.-243A>G		5_prime_UTR_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53967 AN: 151854 Hom.: 14858 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.204 AC: 44455 AN: 217504 Hom.: 5920 Cov.: 0 AF XY: 0.204 AC XY: 23083 AN XY: 113028

Gnomad4 AFR exome AF: 0.769

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.356 AC: 54073 AN: 151972 Hom.: 14906 Cov.: 32 AF XY: 0.353 AC XY: 26224 AN XY: 74270

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.334

Alfa AF: 0.212 Hom.: 8222

Bravo AF: 0.387

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs2236418; hg19: chr10-26505496; COSMIC: COSV52164132; COSMIC: COSV52164132;