ENST00000358510.6:c.2354G>T

Variant names:

• chr2-60452593-C-A
• rs768802721
• ENST00000358510.6:c.2354G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000358510.6(BCL11A):​c.2354G>T​(p.Arg785Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R785P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCL11A ENST00000358510.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 5 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13571891).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000358510.6. 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_001405710.1		c.2456G>T	p.Arg819Leu	missense	Exon 5 of 5	NP_001392639.1
	BCL11A	NM_001363864.1		c.2354G>T	p.Arg785Leu	missense	Exon 4 of 4	NP_001350793.1	A0A2U3TZJ5
	BCL11A	NM_001405716.1		c.2300G>T	p.Arg767Leu	missense	Exon 5 of 5	NP_001392645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL11A	ENST00000358510.6	TSL:1	c.2354G>T	p.Arg785Leu	missense	Exon 4 of 4	ENSP00000351307.5	A0A2U3TZJ5
	BCL11A	ENST00000359629.10	TSL:1	c.704G>T	p.Arg235Leu	missense	Exon 5 of 5	ENSP00000352648.5	Q9H165-3
	BCL11A	ENST00000356842.9	TSL:1	c.2304G>T	p.Ser768Ser	synonymous	Exon 5 of 5	ENSP00000349300.4	Q9H165-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000251 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	18
DANN	Uncertain	0.97
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.038
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.36
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.038
Sift	Uncertain	0.021	D
Sift4G	Benign	0.064	T
Polyphen		0.24	B
Vest4		0.38
MutPred		0.41		Loss of MoRF binding (P = 0.0465)
MVP		0.23
ClinPred		0.16	T
GERP RS		3.1
Mutation Taster		=73/27	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs768802721; hg19: chr2-60679728;