Variant 12-12079498-G-C 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_138723.2(BCL2L14):c.193G>C(p.Glu65Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

BCL2L14
NM_138723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.956

Variant links:

Genes affected

BCL2L14 (HGNC:16657): (BCL2 like 14) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Overexpression of this gene has been shown to induce apoptosis in cells. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported for this gene. [provided by RefSeq, May 2009]

BCL2L14 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=0.16750947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L14	NM_138723.2 linkuse as main transcript	c.193G>C	p.Glu65Gln	missense_variant	2/6	ENST00000308721.9	NP_620049.1	Q9BZR8-1A0A024RAR1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L14	ENST00000308721.9 linkuse as main transcript	c.193G>C	p.Glu65Gln	missense_variant	2/6	1	NM_138723.2	ENSP00000309132.4		Q9BZR8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

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:

0.00000450

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

Sep 09, 2024

The c.193G>C (p.E65Q) alteration is located in exon 2 (coding exon 1) of the BCL2L14 gene. This alteration results from a G to C substitution at nucleotide position 193, causing the glutamic acid (E) at amino acid position 65 to be replaced by a glutamine (Q). 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

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

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

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.20

M_CAP

Benign

0.010

MetaRNN

Benign

0.17

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

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

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.6

.;.;D;N;N;D;.

REVEL

Benign

0.036

Sift

Uncertain

0.015

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

Sift4G

Uncertain

0.031

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

Polyphen

0.99

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

Vest4

0.086

MutPred

0.30

Gain of catalytic residue at W67 (P = 0.001);.;.;Gain of catalytic residue at W67 (P = 0.001);Gain of catalytic residue at W67 (P = 0.001);Gain of catalytic residue at W67 (P = 0.001);Gain of catalytic residue at W67 (P = 0.001);

MVP

0.73

MPC

0.40

ClinPred

0.80

GERP RS

3.2

Varity_R

0.13

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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