chr2-60460824-A-G

Variant names:

• chr2-60460824-A-G
• rs7569946
• NM_022893.4:c.2088T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022893.4(BCL11A):​c.2088T>C​(p.Ser696Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,612,372 control chromosomes in the GnomAD database, including 352,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41375 hom., cov: 34)
  • Exomes 𝑓: 0.65 (311418 hom.)
• Consequence: BCL11A NM_022893.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.80
• Publications: 22 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), PanelApp Australia, ClinGen, Ambry Genetics, G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-60460824-A-G is Benign according to our data. Variant chr2-60460824-A-G is described in ClinVar as [Benign]. Clinvar id is 1276488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL11A	NM_022893.4	c.2088T>C	p.Ser696Ser	synonymous_variant	Exon 4 of 4	ENST00000642384.2	NP_075044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL11A	ENST00000642384.2	c.2088T>C	p.Ser696Ser	synonymous_variant	Exon 4 of 4		NM_022893.4	ENSP00000496168.1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109908 AN: 152080 Hom.: 41311 Cov.: 34

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.702 AC: 174802 AN: 249048 AF XY: 0.691

Gnomad AFR exome AF: 0.914

Gnomad AMR exome AF: 0.850

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.592

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.656

GnomAD4 exome AF: 0.646 AC: 943971 AN: 1460174 Hom.: 311418 Cov.: 98 AF XY: 0.646 AC XY: 469550 AN XY: 726466

African (AFR) AF: 0.909 AC: 30438 AN: 33480

American (AMR) AF: 0.839 AC: 37527 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 14832 AN: 26136

East Asian (EAS) AF: 0.999 AC: 39671 AN: 39700

South Asian (SAS) AF: 0.727 AC: 62664 AN: 86254

European-Finnish (FIN) AF: 0.587 AC: 30354 AN: 51742

Middle Eastern (MID) AF: 0.558 AC: 3218 AN: 5768

European-Non Finnish (NFE) AF: 0.616 AC: 685314 AN: 1111992

Other (OTH) AF: 0.662 AC: 39953 AN: 60380

GnomAD4 genome AF: 0.723 AC: 110027 AN: 152198 Hom.: 41375 Cov.: 34 AF XY: 0.724 AC XY: 53871 AN XY: 74406

African (AFR) AF: 0.906 AC: 37672 AN: 41574

American (AMR) AF: 0.768 AC: 11744 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1941 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5166 AN: 5178

South Asian (SAS) AF: 0.755 AC: 3646 AN: 4830

European-Finnish (FIN) AF: 0.606 AC: 6419 AN: 10590

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41242 AN: 67946

Other (OTH) AF: 0.712 AC: 1505 AN: 2114

Alfa AF: 0.633 Hom.: 42429

Bravo AF: 0.745

Asia WGS AF: 0.886 AC: 3079 AN: 3478

EpiCase AF: 0.610

EpiControl AF: 0.604

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.59
PhyloP100		2.8
PromoterAI		0.025	Neutral
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7569946; hg19: chr2-60687959; COSMIC: COSV59626533; COSMIC: COSV59626533;