12-12090809-T-C

Variant summary

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

The NM_138723.2(BCL2L14):c.638T>C(p.Val213Ala) 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)
• Consequence: BCL2L14 NM_138723.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L14	NM_138723.2	c.638T>C	p.Val213Ala	missense_variant	4/6	ENST00000308721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L14	ENST00000308721.9	c.638T>C	p.Val213Ala	missense_variant	4/6	1	NM_138723.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.638T>C (p.V213A) alteration is located in exon 4 (coding exon 3) of the BCL2L14 gene. This alteration results from a T to C substitution at nucleotide position 638, causing the valine (V) at amino acid position 213 to be replaced by an alanine (A). 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	0.36
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.070	T;T;T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	M;.;M;M;M
MutationTaster	Benign	0.92	D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	0.084	T;T;T;T;D
Polyphen		0.88	P;.;P;P;D
Vest4		0.67
MutPred		0.50		Gain of disorder (P = 0.0406);.;Gain of disorder (P = 0.0406);Gain of disorder (P = 0.0406);Gain of disorder (P = 0.0406);
MVP		0.51
MPC		0.61
ClinPred		0.84	D
GERP RS		4.0
Varity_R		0.099
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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.

Other links and lift over

hg19: chr12-12243743;