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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32
Variant links:
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
GABBR2NM_005458.8 linkc.954_959delTTTCGA p.Asp318_Phe319del disruptive_inframe_deletion Exon 6 of 19 ENST00000259455.4 NP_005449.5 O75899H9NIL8
GABBR2XM_017015331.3 linkc.660_665delTTTCGA p.Asp220_Phe221del disruptive_inframe_deletion Exon 5 of 18 XP_016870820.1
GABBR2XM_005252316.6 linkc.180_185delTTTCGA p.Asp60_Phe61del disruptive_inframe_deletion Exon 4 of 17 XP_005252373.1
GABBR2XM_017015332.3 linkc.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
GABBR2ENST00000259455.4 linkc.954_959delTTTCGA p.Asp318_Phe319del disruptive_inframe_deletion Exon 6 of 19 1 NM_005458.8 ENSP00000259455.2 O75899
GABBR2ENST00000634919.1 linkn.732_737delTTTCGA non_coding_transcript_exon_variant Exon 5 of 6 5
GABBR2ENST00000637410.1 linkn.732_737delTTTCGA non_coding_transcript_exon_variant Exon 6 of 19 5
GABBR2ENST00000477471.1 linkn.*39_*44delTTTCGA downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 08, 2019Experimental 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554709553; hg19: chr9-101235467; API