chr18-63319176-G-C

Variant names:

• chr18-63319176-G-C
• NM_000633.3:c.-289C>G

Variant summary

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

The NM_000633.3(BCL2):​c.-289C>G variant causes a splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCL2 NM_000633.3 splice_region
• Scores: Splicing: ADA: 0.02740
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 5.09

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 (BayesDel_noAF=-0.39).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.-289C>G		splice_region_variant	Exon 1 of 3	ENST00000333681.5	NP_000624.2
BCL2	NM_000633.3	c.-289C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000333681.5	NP_000624.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5	c.-289C>G		splice_region_variant	Exon 1 of 3	1	NM_000633.3	ENSP00000329623.3
BCL2	ENST00000333681.5	c.-289C>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_000633.3	ENSP00000329623.3
BCL2	ENST00000398117.1	c.-510C>G		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000381185.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 33

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Neoplasm Other:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: -

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.027
dbscSNV1_RF	Benign	0.14
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: chr18-60986409;