Variant 19-49667033-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138639.2(BCL2L12):c.122A>G(p.Glu41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BCL2L12
NM_138639.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

BCL2L12 (HGNC:13787): (BCL2 like 12) This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

BCL2L12 links:

BCL2L12 (HGNC:):

BCL2L12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15586832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L12	NM_138639.2 linkuse as main transcript	c.122A>G	p.Glu41Gly	missense_variant	3/7	ENST00000246784.8	NP_619580.2	Q9HB09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L12	ENST00000246784.8 linkuse as main transcript	c.122A>G	p.Glu41Gly	missense_variant	3/7	1	NM_138639.2	ENSP00000246784.4		A0A087WSV0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250528

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135538

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:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461206

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726878

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:

0.00

Gnomad4 OTH exome

AF:

0.0000332

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

Jul 14, 2021

The c.374A>G (p.E125G) alteration is located in exon 3 (coding exon 3) of the BCL2L12 gene. This alteration results from a A to G substitution at nucleotide position 374, causing the glutamic acid (E) at amino acid position 125 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

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

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

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.16

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

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

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.9

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

REVEL

Benign

0.14

Sift

Uncertain

0.019

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

Sift4G

Pathogenic

0.0

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

Polyphen

0.73

P;.;.;.;P;.;.;.

Vest4

0.29

MutPred

0.064

Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);.;Loss of solvent accessibility (P = 0.0387);.;.;.;

MVP

0.52

MPC

0.67

ClinPred

0.37

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.48

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

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