rs1555919960

Variant names:

• chrX-40074947-C-CGT
• rs1555919960
• NM_001123385.2:c.398_399insAC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001123385.2(BCOR):​c.398_399insAC​(p.Ala134ArgfsTer28) variant causes a frameshift 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 (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: BCOR NM_001123385.2 frameshift
• Clinical Significance: Other O:1
• Conservation: PhyloP100: 7.67
• Publications: 1 publications found

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]

BCOR Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 2

  Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, ClinGen, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 10 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123385.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.398_399insAC	p.Ala134ArgfsTer28	frameshift	Exon 4 of 15	NP_001116857.1
	BCOR	NM_001437510.1		c.398_399insAC	p.Ala134ArgfsTer28	frameshift	Exon 4 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.398_399insAC	p.Ala134ArgfsTer28	frameshift	Exon 4 of 14	NP_001425136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.398_399insAC	p.Ala134ArgfsTer28	frameshift	Exon 4 of 15	ENSP00000367705.4
	BCOR	ENST00000397354.7	TSL:1	c.398_399insAC	p.Ala134ArgfsTer28	frameshift	Exon 4 of 15	ENSP00000380512.3
	BCOR	ENST00000378455.8	TSL:1	c.398_399insAC	p.Ala134ArgfsTer28	frameshift	Exon 4 of 14	ENSP00000367716.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 22

ClinVar

Significance:

Submissions summary: Other:1

Revision:

Submissions by phenotype

Adenoid cystic carcinoma Other:1

Nov 13, 2024

Genome Sciences Centre, British Columbia Cancer Agency

Significance:

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

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

Other links and lift over

dbSNP: rs1555919960; hg19: chrX-39934200;