rs1553353022

Variant names:

• chr2-60546163-C-A
• rs1553353022
• NM_022893.4:c.193G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-60546163-C-A
• chr2-60546163-C-G
• chr2-60546163-C-T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_022893.4(BCL11A):​c.193G>T​(p.Glu65*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCL11A NM_022893.4 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.08
• Publications: 1 publications found

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]

BCL11A Gene-Disease associations (from GenCC):

• Dias-Logan syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

ACMG classification

Our verdict: Pathogenic. The variant received 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 2-60546163-C-A is Pathogenic according to our data. Variant chr2-60546163-C-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 559890.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022893.4. 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
	BCL11A	NM_022893.4	MANE Select	c.193G>T	p.Glu65*	stop_gained	Exon 2 of 4	NP_075044.2
	BCL11A	NM_001405708.1		c.193G>T	p.Glu65*	stop_gained	Exon 2 of 5	NP_001392637.1	D9YZW0
	BCL11A	NM_001405709.1		c.193G>T	p.Glu65*	stop_gained	Exon 3 of 5	NP_001392638.1	D9YZW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL11A	ENST00000642384.2	MANE Select	c.193G>T	p.Glu65*	stop_gained	Exon 2 of 4	ENSP00000496168.1	Q9H165-1
	BCL11A	ENST00000335712.11	TSL:1	c.193G>T	p.Glu65*	stop_gained	Exon 2 of 3	ENSP00000338774.7	Q9H165-6
	BCL11A	ENST00000358510.6	TSL:1	c.193G>T	p.Glu65*	stop_gained	Exon 2 of 4	ENSP00000351307.5	A0A2U3TZJ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Dias-Logan syndrome (1)
1	-	-	Marfanoid habitus and intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		6.1
Vest4		0.87
GERP RS		5.8
PromoterAI		-0.026	Neutral
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1553353022; hg19: chr2-60773298;