NM_000633.3:c.338C>T

Variant names:

• chr18-63318329-G-A
• NM_000633.3:c.338C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000633.3(BCL2):​c.338C>T​(p.Ala113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 32)
• Consequence: BCL2 NM_000633.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

Genes affected

BCL2 (HGNC:990): (BCL2 apoptosis regulator) This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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=0.16232178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.338C>T	p.Ala113Val	missense_variant	Exon 2 of 3	ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.338C>T	p.Ala113Val	missense_variant	Exon 2 of 3	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.42	T;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.034	N
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	D;D;.
REVEL	Benign	0.063
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.35	B;B;.
Vest4		0.066
MutPred		0.45		Loss of disorder (P = 0.0796);Loss of disorder (P = 0.0796);Loss of disorder (P = 0.0796);
MVP		0.49
MPC		0.89
ClinPred		0.44	T
GERP RS		0.050
Varity_R		0.57
gMVP		0.79

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.

Other links and lift over

hg19: chr18-60985562; COSMIC: COSV61386273;