chr2-60452670-G-GA

Variant names:

• chr2-60452670-G-GA
• rs113307140
• ENST00000358510.6:c.2281-5_2281-4insT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001405708.1(BCL11A):​c.*3-5dupT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00196 in 1,610,670 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (4 hom.)
• Consequence: BCL11A NM_001405708.1 splice_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 4.15
• 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: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 2-60452670-G-GA is Benign according to our data. Variant chr2-60452670-G-GA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 992483.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00149 (227/152226) while in subpopulation NFE AF = 0.00293 (199/68016). AF 95% confidence interval is 0.00259. There are 0 homozygotes in GnomAd4. There are 98 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 227 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405708.1. 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_001405708.1		c.*3-5dupT		splice_region intron	N/A	NP_001392637.1	D9YZW0
	BCL11A	NM_001405710.1		c.2383-5dupT		splice_region intron	N/A	NP_001392639.1
	BCL11A	NM_001405712.1		c.*3-5dupT		splice_region intron	N/A	NP_001392641.1	Q9H165-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL11A	ENST00000358510.6	TSL:1	c.2281-5_2281-4insT		splice_region intron	N/A	ENSP00000351307.5	A0A2U3TZJ5
	BCL11A	ENST00000356842.9	TSL:1	c.2231-5_2231-4insT		splice_region intron	N/A	ENSP00000349300.4	Q9H165-2
	BCL11A	ENST00000359629.10	TSL:1	c.631-5_631-4insT		splice_region intron	N/A	ENSP00000352648.5	Q9H165-3

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 227 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00144 AC: 361 AN: 250366 AF XY: 0.00146

Gnomad AFR exome AF: 0.000743

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.00269

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00200 AC: 2923 AN: 1458444 Hom.: 4 Cov.: 29 AF XY: 0.00199 AC XY: 1446 AN XY: 725762

African (AFR) AF: 0.000569 AC: 19 AN: 33402

American (AMR) AF: 0.000380 AC: 17 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00102 AC: 88 AN: 86170

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53392

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5760

European-Non Finnish (NFE) AF: 0.00241 AC: 2676 AN: 1108938

Other (OTH) AF: 0.00153 AC: 92 AN: 60264

GnomAD4 genome AF: 0.00149 AC: 227 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74450

African (AFR) AF: 0.000385 AC: 16 AN: 41506

American (AMR) AF: 0.000393 AC: 6 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00293 AC: 199 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00195 Hom.: 0

Bravo AF: 0.00143

EpiCase AF: 0.00294

EpiControl AF: 0.00249

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Dias-Logan syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs113307140; hg19: chr2-60679805;