Variant chr2-111123872-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_138621.5(BCL2L11):c.127A>G(p.Asn43Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,452,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

BCL2L11
NM_138621.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

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:

MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

MIR4435-2HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21614584).

BS2

High AC in GnomAdExome4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L11	NM_138621.5 linkuse as main transcript	c.127A>G	p.Asn43Asp	missense_variant	2/4	ENST00000393256.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L11	ENST00000393256.8 linkuse as main transcript	c.127A>G	p.Asn43Asp	missense_variant	2/4	1	NM_138621.5	P1	O43521-1
MIR4435-2HG	ENST00000645030.2 linkuse as main transcript	n.453-86950T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000823

AC:

AN:

242966

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131380

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:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000207

AC:

AN:

1452336

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

722146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.0000262

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

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

Dec 19, 2022

The c.127A>G (p.N43D) alteration is located in exon 2 (coding exon 1) of the BCL2L11 gene. This alteration results from a A to G substitution at nucleotide position 127, causing the asparagine (N) at amino acid position 43 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;.;.;.;.;.;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.88

D;D;D;D;D;D;D;D

M_CAP

Benign

0.0065

MetaRNN

Benign

0.22

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

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.0

.;N;N;N;N;N;N;.

MutationTaster

Benign

0.99

D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

N;.;.;.;.;.;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.016

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

Sift4G

Uncertain

0.047

D;T;T;D;D;D;T;D

Polyphen

1.0, 0.99

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

Vest4

0.37, 0.46, 0.43, 0.43, 0.44, 0.40

MutPred

0.18

Gain of phosphorylation at T38 (P = 0.1845);Gain of phosphorylation at T38 (P = 0.1845);Gain of phosphorylation at T38 (P = 0.1845);Gain of phosphorylation at T38 (P = 0.1845);Gain of phosphorylation at T38 (P = 0.1845);Gain of phosphorylation at T38 (P = 0.1845);Gain of phosphorylation at T38 (P = 0.1845);Gain of phosphorylation at T38 (P = 0.1845);

MVP

0.42

MPC

0.072

ClinPred

0.64

GERP RS

5.3

Varity_R

0.19

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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