12-12079387-G-C

Variant names:

• chr12-12079387-G-C
• rs142096906
• NM_138723.2:c.82G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138723.2(BCL2L14):​c.82G>C​(p.Ala28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,461,884 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: BCL2L14 NM_138723.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825

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]

ACMG classification

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=0.2656242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L14	NM_138723.2	c.82G>C	p.Ala28Pro	missense_variant	Exon 2 of 6	ENST00000308721.9	NP_620049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L14	ENST00000308721.9	c.82G>C	p.Ala28Pro	missense_variant	Exon 2 of 6	1	NM_138723.2	ENSP00000309132.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251478 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135914

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727242

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: 0.0000324

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T;T;T;T;T;T;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.35	N
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;.;.;.;L;L;L;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.0	.;.;D;D;N;N;D;.
REVEL	Benign	0.15
Sift	Benign	0.064	.;.;T;T;D;D;D;.
Sift4G	Benign	0.14	T;T;T;.;T;T;T;T
Polyphen		0.99	D;.;.;.;D;D;P;.
Vest4		0.45
MutPred		0.46		Gain of catalytic residue at L27 (P = 0);.;Gain of catalytic residue at L27 (P = 0);.;Gain of catalytic residue at L27 (P = 0);Gain of catalytic residue at L27 (P = 0);Gain of catalytic residue at L27 (P = 0);Gain of catalytic residue at L27 (P = 0);
MVP		0.67
MPC		0.60
ClinPred		0.50	D
GERP RS		2.3
Varity_R		0.26
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs142096906; hg19: chr12-12232321;