rs1554709553
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP3
The NM_005458.8(GABBR2):c.954_959delTTTCGA(p.Asp318_Phe319del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Consequence
GABBR2
NM_005458.8 disruptive_inframe_deletion
NM_005458.8 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.32
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 Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_005458.8.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABBR2 | NM_005458.8 | c.954_959delTTTCGA | p.Asp318_Phe319del | disruptive_inframe_deletion | Exon 6 of 19 | ENST00000259455.4 | NP_005449.5 | |
GABBR2 | XM_017015331.3 | c.660_665delTTTCGA | p.Asp220_Phe221del | disruptive_inframe_deletion | Exon 5 of 18 | XP_016870820.1 | ||
GABBR2 | XM_005252316.6 | c.180_185delTTTCGA | p.Asp60_Phe61del | disruptive_inframe_deletion | Exon 4 of 17 | XP_005252373.1 | ||
GABBR2 | XM_017015332.3 | c.180_185delTTTCGA | p.Asp60_Phe61del | disruptive_inframe_deletion | Exon 3 of 16 | XP_016870821.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABBR2 | ENST00000259455.4 | c.954_959delTTTCGA | p.Asp318_Phe319del | disruptive_inframe_deletion | Exon 6 of 19 | 1 | NM_005458.8 | ENSP00000259455.2 | ||
GABBR2 | ENST00000634919.1 | n.732_737delTTTCGA | non_coding_transcript_exon_variant | Exon 5 of 6 | 5 | |||||
GABBR2 | ENST00000637410.1 | n.732_737delTTTCGA | non_coding_transcript_exon_variant | Exon 6 of 19 | 5 | |||||
GABBR2 | ENST00000477471.1 | n.*39_*44delTTTCGA | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
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 | Labcorp Genetics (formerly Invitae), Labcorp | May 08, 2019 | Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has not been reported in the literature in individuals with a GABBR2-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.954_959delTTTCGA, results in the deletion of 2 amino acids of the GABBR2 protein (p.Asp318_Phe319del), but otherwise preserves the integrity of the reading frame. In summary, this variant has uncertain impact on GABBR2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at