14-23309489-A-G

Variant names:

• chr14-23309489-A-G
• rs1950252
• NM_004050.5:c.*524A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004050.5(BCL2L2):​c.*524A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 986,148 control chromosomes in the GnomAD database, including 421,574 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 0.92 (65155 hom., cov: 33)
  • Exomes 𝑓: 0.92 (356419 hom.)
• Consequence: BCL2L2 NM_004050.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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:42959): (BCL2L2-PABPN1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BCL2L2 (BCL2-like 2) and PABPN1 (poly(A) binding protein, nuclear 1) genes on chromosome 14. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L2	NM_004050.5	c.*524A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000250405.10	NP_004041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L2	ENST00000250405.10	c.*524A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_004050.5	ENSP00000250405.6
BCL2L2-PABPN1	ENST00000678502.1	c.432+1290A>G		intron_variant	Intron 3 of 9			ENSP00000503309.1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140625 AN: 152138 Hom.: 65099 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.918

GnomAD4 exome AF: 0.924 AC: 770788 AN: 833892 Hom.: 356419 Cov.: 65 AF XY: 0.924 AC XY: 355913 AN XY: 385140

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.959

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.934

Gnomad4 NFE exome AF: 0.928

Gnomad4 OTH exome AF: 0.914

GnomAD4 genome AF: 0.924 AC: 140739 AN: 152256 Hom.: 65155 Cov.: 33 AF XY: 0.924 AC XY: 68799 AN XY: 74442

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.918

Alfa AF: 0.927 Hom.: 96448

Bravo AF: 0.927

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1950252; hg19: chr14-23778698;