rs886037867

Positions:

• chr2-60461136-G-GCCA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_022893.4(BCL11A):​c.1775_1776insTGG​(p.Gly592_Glu592insGly) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCL11A NM_022893.4 inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.24

Genes affected

BCL11A (HGNC:13221): (BCL11 transcription factor A) This gene encodes a C2H2 type zinc-finger protein by its similarity to the mouse Bcl11a/Evi9 protein. The corresponding mouse gene is a common site of retroviral integration in myeloid leukemia, and may function as a leukemia disease gene, in part, through its interaction with BCL6. During hematopoietic cell differentiation, this gene is down-regulated. It is possibly involved in lymphoma pathogenesis since translocations associated with B-cell malignancies also deregulates its expression. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_022893.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 2-60461136-G-GCCA is Pathogenic according to our data. Variant chr2-60461136-G-GCCA is described in ClinVar as [Pathogenic]. Clinvar id is 253304.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.1775_1776insTGG	p.Gly592_Glu592insGly	inframe_insertion	4/4	ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2	c.1775_1776insTGG	p.Gly592_Glu592insGly	inframe_insertion	4/4		NM_022893.4	ENSP00000496168

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dias-Logan syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 08, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886037867; hg19: chr2-60688271;