rs1555915744

Variant names:

• chrX-40064392-GCAGTGGTCT-G
• rs1555915744
• NM_001123385.2:c.3437_3445delAGACCACTG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_001123385.2(BCOR):​c.3437_3445delAGACCACTG​(p.Glu1146_Thr1148del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: BCOR NM_001123385.2 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.67
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Illumina, Orphanet, ClinGen, Ambry Genetics
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001123385.2.
• PP5: Variant X-40064392-GCAGTGGTCT-G is Pathogenic according to our data. Variant chrX-40064392-GCAGTGGTCT-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 522683.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	NM_001123385.2	MANE Select	c.3437_3445delAGACCACTG	p.Glu1146_Thr1148del	disruptive_inframe_deletion	Exon 7 of 15	NP_001116857.1	Q6W2J9-1
	BCOR	NM_001437510.1		c.3437_3445delAGACCACTG	p.Glu1146_Thr1148del	disruptive_inframe_deletion	Exon 7 of 15	NP_001424439.1
	BCOR	NM_001438207.1		c.3383_3391delAGACCACTG	p.Glu1128_Thr1130del	disruptive_inframe_deletion	Exon 6 of 14	NP_001425136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCOR	ENST00000378444.9	TSL:1 MANE Select	c.3437_3445delAGACCACTG	p.Glu1146_Thr1148del	disruptive_inframe_deletion	Exon 7 of 15	ENSP00000367705.4	Q6W2J9-1
	BCOR	ENST00000397354.7	TSL:1	c.3437_3445delAGACCACTG	p.Glu1146_Thr1148del	disruptive_inframe_deletion	Exon 7 of 15	ENSP00000380512.3	Q6W2J9-2
	BCOR	ENST00000378455.8	TSL:1	c.3383_3391delAGACCACTG	p.Glu1128_Thr1130del	disruptive_inframe_deletion	Exon 6 of 14	ENSP00000367716.4	Q6W2J9-4

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Oculofaciocardiodental syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7
Mutation Taster		=153/47	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1555915744; hg19: chrX-39923645;