chr14-23319887-C-CTT

Position:

• chr14-23319887-C-CTT

Variant summary

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

The NM_001387340.1(BCL2L2-PABPN1):​c.550-2293_550-2292dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,011,254 control chromosomes in the GnomAD database, including 427,549 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (65086 hom., cov: 0)
  • Exomes 𝑓: 0.92 (362463 hom.)
• Consequence: BCL2L2-PABPN1 NM_001387340.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

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 14-23319887-C-CTT is Benign according to our data. Variant chr14-23319887-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1261404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2L2-PABPN1	NM_001387340.1	c.550-2293_550-2292dupTT		intron_variant			NP_001374269.1
BCL2L2-PABPN1	NM_001387341.1	c.528+58_528+59dupTT		intron_variant			NP_001374270.1
BCL2L2-PABPN1	NM_001387342.1	c.528+58_528+59dupTT		intron_variant			NP_001374271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL2L2-PABPN1	ENST00000678502.1	c.528+57_528+58insTT		intron_variant				ENSP00000503309.1
BCL2L2-PABPN1	ENST00000553781.5	c.433-2294_433-2293insTT		intron_variant		2		ENSP00000451320.1
BCL2L2-PABPN1	ENST00000557008.2	c.433-2294_433-2293insTT		intron_variant		5		ENSP00000452479.1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140534 AN: 152090 Hom.: 65029 Cov.: 0

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.915

GnomAD4 exome AF: 0.917 AC: 787588 AN: 859046 Hom.: 362463 AF XY: 0.911 AC XY: 392754 AN XY: 430980

Gnomad4 AFR exome AF: 0.915

Gnomad4 AMR exome AF: 0.964

Gnomad4 ASJ exome AF: 0.942

Gnomad4 EAS exome AF: 0.941

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.958

Gnomad4 NFE exome AF: 0.927

Gnomad4 OTH exome AF: 0.912

GnomAD4 genome AF: 0.924 AC: 140649 AN: 152208 Hom.: 65086 Cov.: 0 AF XY: 0.924 AC XY: 68748 AN XY: 74404

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.915

Alfa AF: 0.925 Hom.: 6979

Bravo AF: 0.926

Asia WGS AF: 0.836 AC: 2906 AN: 3478

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

Mar 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10640563; hg19: chr14-23789096;