Genetic Variant BCL2L2:c.*524A>T (chr14-23309489-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004050.5(BCL2L2):c.*524A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BCL2L2
NM_004050.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0830

Publications

11 publications found

Variant links:

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 links:

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]

BCL2L2-PABPN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004050.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCL2L2	NM_004050.5	MANE Select	c.*524A>T	3_prime_UTR	Exon 4 of 4	NP_004041.2	Q92843-1
BCL2L2	NM_001199839.2		c.*524A>T	3_prime_UTR	Exon 4 of 4	NP_001186768.2	Q92843-1
BCL2L2-PABPN1	NM_001387340.1		c.549+557A>T	intron	N/A	NP_001374269.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCL2L2	ENST00000250405.10	TSL:1 MANE Select	c.*524A>T	3_prime_UTR	Exon 4 of 4	ENSP00000250405.6	Q92843-1
BCL2L2-PABPN1	ENST00000553781.5	TSL:2	c.432+1290A>T	intron	N/A	ENSP00000451320.1	Q92843-2
BCL2L2	ENST00000678311.1		c.*524A>T	3_prime_UTR	Exon 4 of 4	ENSP00000504570.1	Q92843-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152152

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

833896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

385140

African (AFR)

AF:

0.00

AC:

AN:

15818

American (AMR)

AF:

0.00

AC:

AN:

1000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5182

East Asian (EAS)

AF:

0.00

AC:

AN:

3648

South Asian (SAS)

AF:

0.00

AC:

AN:

16472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

762402

Other (OTH)

AF:

0.00

AC:

AN:

27358

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.083

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over