rs2165607

Variant names:

• chr4-46398204-T-C
• rs2165607
• ENST00000510861.5:c.-10-9488A>G

Variant summary

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

The ENST00000510861.5(GABRA2):​c.-10-9488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0627 in 152,250 control chromosomes in the GnomAD database, including 400 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 0.063 (400 hom., cov: 32)
• Consequence: GABRA2 ENST00000510861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 1 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

ENSG00000249330 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000510861.5	c.-10-9488A>G		intron_variant	Intron 1 of 9	5		ENSP00000421828.1
ENSG00000249330	ENST00000502455.2	n.438+7196T>C		intron_variant	Intron 2 of 2	4
ENSG00000249330	ENST00000651612.1	n.386+7196T>C		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9562 AN: 152132 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0627 AC: 9545 AN: 152250 Hom.: 400 Cov.: 32 AF XY: 0.0649 AC XY: 4829 AN XY: 74438

African (AFR) AF: 0.0242 AC: 1007 AN: 41568

American (AMR) AF: 0.0869 AC: 1328 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 329 AN: 3472

East Asian (EAS) AF: 0.0468 AC: 242 AN: 5174

South Asian (SAS) AF: 0.175 AC: 843 AN: 4822

European-Finnish (FIN) AF: 0.0587 AC: 623 AN: 10610

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4978 AN: 68006

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0682 Hom.: 717

Bravo AF: 0.0613

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.097
DANN	Benign	0.71
PhyloP100		-1.3
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: rs2165607; hg19: chr4-46400221;