Variant chr2-111123830-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138621.5(BCL2L11):c.85A>G(p.Arg29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BCL2L11
NM_138621.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L11	NM_138621.5 linkuse as main transcript	c.85A>G	p.Arg29Gly	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.85A>G	p.Arg29Gly	missense_variant	2/4	1	NM_138621.5	P1	O43521-1
MIR4435-2HG	ENST00000645030.2 linkuse as main transcript	n.453-86908T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1389992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685264

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 17, 2021

The c.85A>G (p.R29G) 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 85, causing the arginine (R) at amino acid position 29 to be replaced by a glycine (G). 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

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

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

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.61

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.62

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

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.81

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

MutationTaster

Benign

0.98

D;D;D;D;D;N

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-7.0

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

REVEL

Uncertain

0.32

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

0.99, 0.99, 0.99

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

Vest4

0.69, 0.71, 0.69, 0.76, 0.73, 0.79, 0.79, 0.78, 0.78, 0.63, 0.76, 0.71

MutPred

0.59

Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);.;

MVP

0.62

MPC

0.35

ClinPred

0.99

GERP RS

2.6

Varity_R

0.77

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over