chr2-60452594-G-C

Variant names:

• chr2-60452594-G-C
• rs1265922527
• ENST00000358510.6:c.2353C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001405710.1(BCL11A):​c.2455C>G​(p.Arg819Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R819P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: BCL11A NM_001405710.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17
• 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: Labcorp Genetics (formerly Invitae), Illumina, ClinGen, PanelApp Australia, Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405710.1. 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.2455C>G	p.Arg819Gly	missense	Exon 5 of 5	NP_001392639.1
	BCL11A	NM_001363864.1		c.2353C>G	p.Arg785Gly	missense	Exon 4 of 4	NP_001350793.1	A0A2U3TZJ5
	BCL11A	NM_001405716.1		c.2299C>G	p.Arg767Gly	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.2353C>G	p.Arg785Gly	missense	Exon 4 of 4	ENSP00000351307.5	A0A2U3TZJ5
	BCL11A	ENST00000356842.9	TSL:1	c.2303C>G	p.Ser768Trp	missense	Exon 5 of 5	ENSP00000349300.4	Q9H165-2
	BCL11A	ENST00000359629.10	TSL:1	c.703C>G	p.Arg235Gly	missense	Exon 5 of 5	ENSP00000352648.5	Q9H165-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461708 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Dias-Logan syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.2	T
PhyloP100		6.2
PROVEAN	Benign	0.16	N
REVEL	Benign	0.13
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.054	T
Polyphen		0.24	B
Vest4		0.28
MutPred		0.33		Loss of solvent accessibility (P = 0.0159)
MVP		0.52
ClinPred		0.66	D
GERP RS		5.9
Mutation Taster		=56/44	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1265922527; hg19: chr2-60679729;