chr2-60546217-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3PP5

The NM_022893.4(BCL11A):​c.139A>C​(p.Thr47Pro) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

BCL11A
NM_022893.4 missense

Scores

8
8
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_022893.4
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 3.6065 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, Dias-Logan syndrome.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.793
PP5
Variant 2-60546217-T-G is Pathogenic according to our data. Variant chr2-60546217-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 253300.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-60546217-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL11ANM_022893.4 linkuse as main transcriptc.139A>C p.Thr47Pro missense_variant 2/4 ENST00000642384.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL11AENST00000642384.2 linkuse as main transcriptc.139A>C p.Thr47Pro missense_variant 2/4 NM_022893.4 Q9H165-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Dias-Logan syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMSep 08, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.88
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
32
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.70
.;.;.;.;.;.;.;D;.;.;.;.;.;.;.
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
1.0
.;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.064
D
MetaRNN
Pathogenic
0.79
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Uncertain
2.6
.;M;M;.;.;.;.;M;M;.;.;.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-4.3
.;D;D;.;.;.;D;.;D;.;.;.;.;.;.
REVEL
Uncertain
0.60
Sift
Uncertain
0.0010
.;D;D;.;.;.;D;.;D;.;.;.;.;.;.
Sift4G
Uncertain
0.0020
.;D;D;.;.;.;D;.;D;.;.;.;D;.;.
Polyphen
1.0, 1.0
.;.;D;.;.;.;.;D;D;.;.;.;.;.;.
Vest4
0.68, 0.81, 0.66, 0.68, 0.81
MutPred
0.48
Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);.;Gain of disorder (P = 0.0324);.;Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);.;Gain of disorder (P = 0.0324);.;Gain of disorder (P = 0.0324);.;Gain of disorder (P = 0.0324);
MVP
0.71
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.81
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886037864; hg19: chr2-60773352; API