BCL11A p.Ser696Arg

Variant names:

• chr2-60460826-T-G
• NM_022893.4:c.2086A>C
• BCL11A p.Ser696Arg

Your query was ambiguous. Multiple possible variants found:

• chr2-60460826-T-G
• chr2-60460824-A-T
• chr2-60460824-A-C
• chr2-60460824-ACT-GCG
• chr2-60460824-ACT-TCG
• chr2-60460824-ACT-CCG

Variant summary

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

The NM_022893.4(BCL11A):​c.2086A>C​(p.Ser696Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S696S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCL11A NM_022893.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• Publications: 0 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: G2P, Illumina, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2086A>C	p.Ser696Arg	missense	Exon 4 of 4	NP_075044.2
	BCL11A	NM_001405708.1		c.2086A>C	p.Ser696Arg	missense	Exon 4 of 5	NP_001392637.1	D9YZW0
	BCL11A	NM_001405709.1		c.2086A>C	p.Ser696Arg	missense	Exon 5 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.2086A>C	p.Ser696Arg	missense	Exon 4 of 4	ENSP00000496168.1	Q9H165-1
	BCL11A	ENST00000335712.11	TSL:1	c.1984A>C	p.Ser662Arg	missense	Exon 3 of 3	ENSP00000338774.7	Q9H165-6
	BCL11A	ENST00000358510.6	TSL:1	c.1984A>C	p.Ser662Arg	missense	Exon 3 of 4	ENSP00000351307.5	A0A2U3TZJ5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
PromoterAI		0.0098	Neutral
Varity_R		0.77
gMVP		0.92
Mutation Taster		=34/66	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-60687961;