rs766299103

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138621.5(BCL2L11):​c.82C>G​(p.Leu28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 1,540,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BCL2L11
NM_138621.5 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21
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]
MIR4435-2HG (HGNC:35163): (MIR4435-2 host gene)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3094386).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCL2L11NM_138621.5 linkc.82C>G p.Leu28Val missense_variant Exon 2 of 4 ENST00000393256.8 NP_619527.1 O43521-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCL2L11ENST00000393256.8 linkc.82C>G p.Leu28Val missense_variant Exon 2 of 4 1 NM_138621.5 ENSP00000376943.2 O43521-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000523
AC:
1
AN:
191286
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
101674
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000434
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000144
AC:
2
AN:
1387970
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
684024
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000616
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
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000435
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.82C>G (p.L28V) alteration is located in exon 2 (coding exon 1) of the BCL2L11 gene. This alteration results from a C to G substitution at nucleotide position 82, causing the leucine (L) at amino acid position 28 to be replaced by a valine (V). 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
0.13
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.073
.;.;T;.;.;.;.;.;.;.;.;D;T;.;.;.;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.31
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
0.69
.;N;.;N;N;N;N;N;N;N;N;N;.;N;N;N;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.7
D;D;N;N;.;.;.;.;.;.;.;N;D;D;.;.;D
REVEL
Benign
0.16
Sift
Uncertain
0.019
D;D;D;D;.;.;.;.;.;.;.;D;D;D;.;.;D
Sift4G
Benign
0.086
T;D;D;T;T;D;T;T;T;T;D;T;T;D;.;.;D
Polyphen
1.0, 0.99, 1.0
.;D;.;D;.;.;.;D;.;.;.;D;.;D;.;.;.
Vest4
0.35, 0.41, 0.35, 0.38, 0.41, 0.43, 0.39, 0.39, 0.37, 0.28, 0.34, 0.37
MutPred
0.52
Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);Loss of glycosylation at P25 (P = 0.2191);.;
MVP
0.35
MPC
0.32
ClinPred
0.63
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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.

Other links and lift over

dbSNP: rs766299103; hg19: chr2-111881404; API