Variant chr4-46250318-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

The NM_000807.4(GABRA2):c.1346T>C(p.Val449Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GABRA2
NM_000807.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.15

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GABRA2. . Gene score misZ 3.1277 (greater than the threshold 3.09). Trascript score misZ 3.4041 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 78, undetermined early-onset epileptic encephalopathy.

BP4

Computational evidence support a benign effect (MetaRNN=0.08097023).

BP6

Variant 4-46250318-A-G is Benign according to our data. Variant chr4-46250318-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1349771.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4 linkuse as main transcript	c.1346T>C	p.Val449Ala	missense_variant	10/10	ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9 linkuse as main transcript	c.1346T>C	p.Val449Ala	missense_variant	10/10	1	NM_000807.4	P2	P47869-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456936

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724742

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.083

T;T;T;T;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

0.067

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

.;.;.;T;T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.081

T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.41

N;N;N;N;.;.

MutationTaster

Benign

0.96

N;N;N;N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.49

N;N;N;N;.;N

REVEL

Benign

0.28

Sift

Benign

0.16

T;T;T;T;.;T

Sift4G

Benign

0.61

T;T;T;T;T;T

Polyphen

0.0020

B;B;B;B;.;.

Vest4

0.028

MutPred

0.20

Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);.;.;

MVP

0.41

MPC

0.29

ClinPred

0.57

GERP RS

5.8

Varity_R

0.059

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over