rs3210043

chr14-23310668-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004050.5(BCL2L2):c.*1703C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,136,690 control chromosomes in the GnomAD database, including 12,985 homozygotes. 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: 𝑓 0.11 (1198 hom., cov: 32)
  • Exomes 𝑓: 0.15 (11787 hom.)
• Consequence: BCL2L2 NM_004050.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

BCL2L2 (HGNC:995): (BCL2 like 2) This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult spermatogenesis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream PABPN1 (poly(A) binding protein, nuclear 1) gene. [provided by RefSeq, Dec 2010]

BCL2L2-PABPN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCL2L2	NM_004050.5	c.*1703C>A		3_prime_UTR_variant	4/4	ENST00000250405.10
BCL2L2-PABPN1	NM_001387343.1	c.432+2469C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL2L2	ENST00000250405.10	c.*1703C>A		3_prime_UTR_variant	4/4	1	NM_004050.5	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16750 AN: 152034 Hom.: 1193 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.149 AC: 146979 AN: 984538 Hom.: 11787 Cov.: 32 AF XY: 0.147 AC XY: 68581 AN XY: 467886

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.0549

Gnomad4 SAS exome AF: 0.0370

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.110 AC: 16760 AN: 152152 Hom.: 1198 Cov.: 32 AF XY: 0.107 AC XY: 7991 AN XY: 74384

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.135

Alfa AF: 0.150 Hom.: 1734

Bravo AF: 0.108

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	15
Dann	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs3210043; hg19: chr14-23779877; COSMIC: COSV105859652; COSMIC: COSV105859652;