14-23309489-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000250405.10(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 ENST00000250405.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000250405.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L2	NM_004050.5	MANE Select	c.*524A>G		3_prime_UTR	Exon 4 of 4	NP_004041.2
	BCL2L2	NM_001199839.2		c.*524A>G		3_prime_UTR	Exon 4 of 4	NP_001186768.2
	BCL2L2-PABPN1	NM_001387340.1		c.549+557A>G		intron	N/A	NP_001374269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL2L2	ENST00000250405.10	TSL:1 MANE Select	c.*524A>G		3_prime_UTR	Exon 4 of 4	ENSP00000250405.6
	BCL2L2-PABPN1	ENST00000553781.5	TSL:2	c.432+1290A>G		intron	N/A	ENSP00000451320.1
	BCL2L2	ENST00000678311.1		c.*524A>G		3_prime_UTR	Exon 4 of 4	ENSP00000504570.1

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

African (AFR) AF: 0.920 AC: 14551 AN: 15818

American (AMR) AF: 0.959 AC: 959 AN: 1000

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 4906 AN: 5182

East Asian (EAS) AF: 0.948 AC: 3457 AN: 3648

South Asian (SAS) AF: 0.771 AC: 12701 AN: 16472

European-Finnish (FIN) AF: 0.934 AC: 368 AN: 394

Middle Eastern (MID) AF: 0.937 AC: 1520 AN: 1622

European-Non Finnish (NFE) AF: 0.928 AC: 707315 AN: 762400

Other (OTH) AF: 0.914 AC: 25011 AN: 27356

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

African (AFR) AF: 0.914 AC: 37984 AN: 41538

American (AMR) AF: 0.934 AC: 14294 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3275 AN: 3472

East Asian (EAS) AF: 0.953 AC: 4923 AN: 5168

South Asian (SAS) AF: 0.762 AC: 3677 AN: 4824

European-Finnish (FIN) AF: 0.964 AC: 10244 AN: 10622

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63233 AN: 68016

Other (OTH) AF: 0.918 AC: 1936 AN: 2110

Alfa AF: 0.927 Hom.: 132623

Bravo AF: 0.927

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.083
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1950252; hg19: chr14-23778698;