ENST00000639111:c.-268C>A

Variant names:

• chr5-162067732-C-A
• rs886060375
• ENST00000639111.2:c.-268C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000639111.2(GABRG2):​c.-268C>A variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABRG2 ENST00000639111.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89
• Publications: 0 publications found

Genes affected

GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRG2 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 74

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 8

  Inheritance: AD Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• generalized epilepsy with febrile seizures plus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• self-limited epilepsy with centrotemporal spikes

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000639111.2. 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
	GABRG2	NM_198903.2		c.-268C>A		5_prime_UTR	Exon 1 of 11	NP_944493.2	P18507-3
	GABRG2	NM_001375343.1		c.-268C>A		5_prime_UTR	Exon 1 of 10	NP_001362272.1	A0A1X7SBZ8
	GABRG2	NM_001375344.1		c.-268C>A		5_prime_UTR	Exon 1 of 11	NP_001362273.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG2	ENST00000639111.2	TSL:1	c.-268C>A		5_prime_UTR	Exon 1 of 9	ENSP00000492125.2	P18507-1
	GABRG2	ENST00000943443.1		c.-268C>A		5_prime_UTR	Exon 1 of 10	ENSP00000613502.1
	GABRG2	ENST00000638772.1	TSL:5	c.-268C>A		5_prime_UTR	Exon 1 of 8	ENSP00000491557.1	A0A1W2PPS4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 457764 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 242902

African (AFR) AF: 0.00 AC: 0 AN: 12560

American (AMR) AF: 0.00 AC: 0 AN: 18846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13806

East Asian (EAS) AF: 0.00 AC: 0 AN: 31542

South Asian (SAS) AF: 0.00 AC: 0 AN: 45152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2000

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 277654

Other (OTH) AF: 0.00 AC: 0 AN: 26506

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.89
PhyloP100		2.9
PromoterAI		0.0098	Neutral

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: rs886060375; hg19: chr5-161494738;