5-162103379-T-C

Variant names:

• chr5-162103379-T-C
• rs211032
• NM_198904.4:c.632-510T>C

Variant summary

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

The NM_198903.2(GABRG2):​c.752-510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 158,236 control chromosomes in the GnomAD database, including 38,637 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 0.70 (37103 hom., cov: 33)
  • Exomes 𝑓: 0.70 (1534 hom.)
• Consequence: GABRG2 NM_198903.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492
• Publications: 1 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: Ambry Genetics, G2P, 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198903.2. 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_198904.4	MANE Select	c.632-510T>C		intron	N/A	NP_944494.1
	GABRG2	NM_198903.2		c.752-510T>C		intron	N/A	NP_944493.2
	GABRG2	NM_001375343.1		c.752-510T>C		intron	N/A	NP_001362272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG2	ENST00000639213.2	TSL:1 MANE Select	c.632-510T>C		intron	N/A	ENSP00000491909.2
	GABRG2	ENST00000414552.6	TSL:1	c.752-510T>C		intron	N/A	ENSP00000410732.2
	GABRG2	ENST00000639111.2	TSL:1	c.632-510T>C		intron	N/A	ENSP00000492125.2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 106024 AN: 152022 Hom.: 37086 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.698 AC: 4257 AN: 6096 Hom.: 1534 Cov.: 0 AF XY: 0.704 AC XY: 2229 AN XY: 3164

African (AFR) AF: 0.625 AC: 20 AN: 32

American (AMR) AF: 0.772 AC: 1011 AN: 1310

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 24 AN: 36

East Asian (EAS) AF: 0.564 AC: 177 AN: 314

South Asian (SAS) AF: 0.734 AC: 571 AN: 778

European-Finnish (FIN) AF: 0.672 AC: 43 AN: 64

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.677 AC: 2257 AN: 3334

Other (OTH) AF: 0.677 AC: 153 AN: 226

GnomAD4 genome AF: 0.697 AC: 106085 AN: 152140 Hom.: 37103 Cov.: 33 AF XY: 0.700 AC XY: 52073 AN XY: 74348

African (AFR) AF: 0.685 AC: 28443 AN: 41536

American (AMR) AF: 0.761 AC: 11622 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3505 AN: 5168

South Asian (SAS) AF: 0.753 AC: 3632 AN: 4822

European-Finnish (FIN) AF: 0.711 AC: 7517 AN: 10566

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.691 AC: 46970 AN: 67988

Other (OTH) AF: 0.699 AC: 1476 AN: 2112

Alfa AF: 0.698 Hom.: 4803

Bravo AF: 0.701

Asia WGS AF: 0.724 AC: 2516 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		0.49
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: rs211032; hg19: chr5-161530385; COSMIC: COSV62716427; COSMIC: COSV62716427;