rs771637982
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_005458.8(GABBR2):c.2776_2777insCCC(p.Pro925dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00000902 in 1,441,334 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Consequence
GABBR2
NM_005458.8 inframe_insertion
NM_005458.8 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.53
Genes affected
GABBR2 (HGNC:4507): (gamma-aminobutyric acid type B receptor subunit 2) The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_005458.8. Strenght limited to Supporting due to length of the change: 1aa.
BS2
?
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABBR2 | NM_005458.8 | c.2776_2777insCCC | p.Pro925dup | inframe_insertion | 19/19 | ENST00000259455.4 | |
GABBR2 | XM_005252316.6 | c.2002_2003insCCC | p.Pro667dup | inframe_insertion | 17/17 | ||
GABBR2 | XM_017015331.3 | c.2482_2483insCCC | p.Pro827dup | inframe_insertion | 18/18 | ||
GABBR2 | XM_017015332.3 | c.2002_2003insCCC | p.Pro667dup | inframe_insertion | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABBR2 | ENST00000259455.4 | c.2776_2777insCCC | p.Pro925dup | inframe_insertion | 19/19 | 1 | NM_005458.8 | P1 | |
GABBR2 | ENST00000637410.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152008Hom.: 1 Cov.: 31
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GnomAD4 exome AF: 0.00000233 AC: 3AN: 1289326Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 631306
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GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 152008Hom.: 1 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74232
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epileptic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | This variant, c.2774_2776dup, results in the insertion of 1 amino acid(s) of the GABBR2 protein (p.Pro925dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs771637982, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GABBR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 462136). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at