Variant 2-60452593-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000358510.6(BCL11A):c.2354G>C(p.Arg785Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R785G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BCL11A
ENST00000358510.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.365

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), BCL11A. . Gene score misZ 3.835 (greater than the threshold 3.09). Trascript score misZ 3.2296 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, Dias-Logan syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.13367239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
BCL11A	NM_001405710.1 linkuse as main transcript	c.2456G>C	p.Arg819Pro	missense_variant	5/5	NP_001392639.1
BCL11A	NM_001363864.1 linkuse as main transcript	c.2354G>C	p.Arg785Pro	missense_variant	4/4	NP_001350793.1
BCL11A	NM_001405716.1 linkuse as main transcript	c.2300G>C	p.Arg767Pro	missense_variant	5/5	NP_001392645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
BCL11A	ENST00000358510.6 linkuse as main transcript	c.2354G>C	p.Arg785Pro	missense_variant	4/4	1	ENSP00000351307
BCL11A	ENST00000359629.10 linkuse as main transcript	c.704G>C	p.Arg235Pro	missense_variant	5/5	1	ENSP00000352648	Q9H165-3
BCL11A	ENST00000356842.9 linkuse as main transcript	c.2304G>C	p.Ser768=	synonymous_variant	5/5	1	ENSP00000349300	Q9H165-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

BCL11A: PM2, PP2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.065

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.65

.;T;T;T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

D;D;N;N

PROVEAN

Benign

1.8

.;N;.;.;.;.

REVEL

Benign

0.068

Sift

Uncertain

0.017

.;D;.;.;.;.

Sift4G

Uncertain

0.051

.;T;.;.;.;.

Polyphen

0.0040

.;B;.;.;.;.

Vest4

0.21

MutPred

0.34

.;.;.;.;.;Loss of MoRF binding (P = 0.0402);

MVP

0.24

ClinPred

0.15

GERP RS

3.1

Splicing

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over