18-63318489-C-T

Variant names:

• chr18-63318489-C-T
• NM_000633.3:c.178G>A

Variant summary

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

The NM_000633.3(BCL2):​c.178G>A​(p.Ala60Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCL2 NM_000633.3 missense
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 0.749

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=0.12674206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2	NM_000633.3	c.178G>A	p.Ala60Thr	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.178G>A	p.Ala60Thr	missense_variant	Exon 2 of 3	1	NM_000633.3	ENSP00000329623.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.37e-7 AC: 1 AN: 1356438 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 669428

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: 9.33e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.35	T;T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.50	.;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L;L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.54	N;N;.
REVEL	Benign	0.11
Sift	Benign	0.25	T;T;.
Sift4G	Uncertain	0.049	D;D;T
Polyphen		0.18	B;B;.
Vest4		0.17
MutPred		0.21		Gain of glycosylation at A60 (P = 0.0017);Gain of glycosylation at A60 (P = 0.0017);Gain of glycosylation at A60 (P = 0.0017);
MVP		0.46
MPC		0.85
ClinPred		0.53	D
GERP RS		3.2
Varity_R		0.073
gMVP		0.27

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: chr18-60985722; COSMIC: COSV61388556;