rs1555915763
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001123385.2(BCOR):c.3410_3411delAA(p.Lys1137fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 24)
Consequence
BCOR
NM_001123385.2 frameshift
NM_001123385.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.66
Genes affected
BCOR (HGNC:20893): (BCL6 corepressor) The protein encoded by this gene was identified as an interacting corepressor of BCL6, a POZ/zinc finger transcription repressor that is required for germinal center formation and may influence apoptosis. This protein selectively interacts with the POZ domain of BCL6, but not with eight other POZ proteins. Specific class I and II histone deacetylases (HDACs) have been shown to interact with this protein, which suggests a possible link between the two classes of HDACs. Several transcript variants encoding different isoforms have been found for this gene. A pseudogene of this gene is found on chromosome Y.[provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-40064426-CTT-C is Pathogenic according to our data. Variant chrX-40064426-CTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 465159.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
24
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
BCOR-related disorder Pathogenic:1
| Likely pathogenic, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2024 | The BCOR c.3410_3411delAA variant is predicted to result in a frameshift and premature protein termination (p.Lys1137Serfs*4). To our knowledge, this variant has not been reported in the literature. Loss of function variants in BCOR are known to cause oculofaciocardiodental (OFCD) syndrome in females (Hilton et al. 2009. PubMed ID: 19367324). This variant has not been reported in a large population database, indicating this variant is rare. In summary, we interpret this variant as likely pathogenic. - |
Oculofaciocardiodental syndrome Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2017 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in BCOR are known to be pathogenic (PMID: 15004558, 19367324). This sequence change deletes 2 nucleotides from exon 7 of the BCOR mRNA (c.3410_3411delAA), causing a frameshift at codon 1137. This creates a premature translational stop signal (p.Lys1137Serfs*4) and is expected to result in an absent or disrupted protein product. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at