14-23320430-A-AG

Position:

• chr14-23320430-A-AG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001387340.1(BCL2L2-PABPN1):​c.550-1746dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,276 control chromosomes in the GnomAD database, including 255 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.048 (255 hom., cov: 32)
• Consequence: BCL2L2-PABPN1 NM_001387340.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410

Genes affected

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 -10 ACMG points.

• BP6: Variant 14-23320430-A-AG is Benign according to our data. Variant chr14-23320430-A-AG is described in ClinVar as [Benign]. Clinvar id is 1262184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L2-PABPN1	NM_001387340.1	c.550-1746dupG		intron_variant			NP_001374269.1
BCL2L2-PABPN1	NM_001387341.1	c.528+605dupG		intron_variant			NP_001374270.1
BCL2L2-PABPN1	NM_001387342.1	c.528+605dupG		intron_variant			NP_001374271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L2-PABPN1	ENST00000678502.1	c.528+600_528+601insG		intron_variant				ENSP00000503309.1
BCL2L2-PABPN1	ENST00000553781.5	c.433-1751_433-1750insG		intron_variant		2		ENSP00000451320.1
BCL2L2-PABPN1	ENST00000557008.2	c.433-1751_433-1750insG		intron_variant		5		ENSP00000452479.1

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7246 AN: 152158 Hom.: 255 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0435

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0476 AC: 7251 AN: 152276 Hom.: 255 Cov.: 32 AF XY: 0.0468 AC XY: 3486 AN XY: 74452

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0765

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0431

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0606 Hom.: 39

Bravo AF: 0.0451

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs147639247; hg19: chr14-23789639;