NM_000807.4:c.1220C>T

Variant names:

• chr4-46250444-G-A
• rs370262263
• NM_000807.4:c.1220C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000807.4(GABRA2):​c.1220C>T​(p.Ala407Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GABRA2 NM_000807.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14343256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.1220C>T	p.Ala407Val	missense_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.1220C>T	p.Ala407Val	missense_variant	Exon 10 of 10	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;T;T;T;T;T
Eigen	Benign	0.091
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	.;.;.;D;D;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.81	L;L;L;L;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.59	N;N;N;N;.;N
REVEL	Uncertain	0.31
Sift	Benign	0.28	T;T;T;T;.;T
Sift4G	Benign	0.34	T;T;T;T;T;T
Polyphen		0.24	B;B;B;B;.;.
Vest4		0.22
MutPred		0.44		Gain of glycosylation at T410 (P = 0.0298);Gain of glycosylation at T410 (P = 0.0298);Gain of glycosylation at T410 (P = 0.0298);Gain of glycosylation at T410 (P = 0.0298);.;.;
MVP		0.57
MPC		0.31
ClinPred		0.44	T
GERP RS		6.0
Varity_R		0.17
gMVP		0.38

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: rs370262263; hg19: chr4-46252461;