GABRA2 p.Lys132Lys

Variant names:

• chr4-46312575-T-T
• NM_000807.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr4-46312576--
• chr4-46312576-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000807.4(GABRA2):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABRA2 NM_000807.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 0 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, G2P, Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000807.4. 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
	GABRA2	NM_000807.4	MANE Select	c.		exon_region	Exon 5 of 10	NP_000798.2	P47869-1
	GABRA2	NM_001330690.2		c.		exon_region	Exon 5 of 11	NP_001317619.1	E9PBQ7
	GABRA2	NM_001377144.1		c.		exon_region	Exon 5 of 11	NP_001364073.1	E9PBQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA2	ENST00000381620.9	TSL:1 MANE Select	c.		exon_region	Exon 5 of 10	ENSP00000371033.4	P47869-1
	GABRA2	ENST00000515082.5	TSL:1	c.		exon_region	Exon 5 of 9	ENSP00000423840.1	G5E9Z6
	GABRA2	ENST00000507069.5	TSL:3	c.		exon_region	Exon 4 of 10	ENSP00000427603.1	E9PBQ7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11

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

hg19: chr4-46314592;