chr2-111123839-G-A

Position:

chr2-111123839-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_138621.5(BCL2L11):c.94G>A(p.Ala32Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000172 in 1,559,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

BCL2L11
NM_138621.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44

Variant links:

Genes affected

BCL2L11 (HGNC:994): (BCL2 like 11) The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]

BCL2L11 links:

BCL2L11 (HGNC:):

BCL2L11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4003766).

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L11	NM_138621.5 linkuse as main transcript	c.94G>A	p.Ala32Thr	missense_variant	2/4	ENST00000393256.8	NP_619527.1	O43521-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L11	ENST00000393256.8 linkuse as main transcript	c.94G>A	p.Ala32Thr	missense_variant	2/4	1	NM_138621.5	ENSP00000376943.2		O43521-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000580

AC:

AN:

206772

Hom.:

AF XY:

0.0000723

AC XY:

AN XY:

110712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000180

AC:

253

AN:

1407382

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

126

AN XY:

695676

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000225

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000120

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.94G>A (p.A32T) alteration is located in exon 2 (coding exon 1) of the BCL2L11 gene. This alteration results from a G to A substitution at nucleotide position 94, causing the alanine (A) at amino acid position 32 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

.;.;T;.;.;.;.;.;.;.;.;D;T;.;.;.;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D

M_CAP

Benign

0.0065

MetaRNN

Benign

0.40

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.81

.;L;.;L;L;L;L;L;L;L;L;L;.;L;L;L;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.0

D;D;D;D;.;.;.;.;.;.;.;D;D;D;.;.;D

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

D;D;D;D;.;.;.;.;.;.;.;D;D;D;.;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;.;D

Polyphen

1.0, 1.0, 1.0

.;D;.;D;.;.;.;D;.;.;.;D;.;D;.;.;.

Vest4

0.80, 0.78, 0.62, 0.60, 0.72, 0.69, 0.62, 0.63, 0.62, 0.55, 0.59, 0.81

MVP

0.42

MPC

0.31

ClinPred

0.77

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over