rs572227

Variant names:

• chr4-46249376-T-C
• rs572227
• NM_000807.4:c.*932A>G

Variant summary

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

The NM_000807.4(GABRA2):​c.*932A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 150,866 control chromosomes in the GnomAD database, including 29,832 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 0.62 (29832 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: GABRA2 NM_000807.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 7 publications found

Genes affected

GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

GABRA2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 78

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.*932A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.*932A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 93871 AN: 150748 Hom.: 29817 Cov.: 30

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.623

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.623 AC: 93926 AN: 150866 Hom.: 29832 Cov.: 30 AF XY: 0.623 AC XY: 45889 AN XY: 73668

African (AFR) AF: 0.725 AC: 29928 AN: 41270

American (AMR) AF: 0.551 AC: 8305 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2396 AN: 3448

East Asian (EAS) AF: 0.549 AC: 2768 AN: 5042

South Asian (SAS) AF: 0.778 AC: 3741 AN: 4806

European-Finnish (FIN) AF: 0.599 AC: 6305 AN: 10530

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38432 AN: 67402

Other (OTH) AF: 0.624 AC: 1303 AN: 2088

Alfa AF: 0.595 Hom.: 13833

Bravo AF: 0.617

Asia WGS AF: 0.652 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.059
DANN	Benign	0.51
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs572227; hg19: chr4-46251393;