Variant 1-161223055-CCACACA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The ENST00000367990.7(APOA2):c.53-11_53-6delTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.32 ( 7601 hom., cov: 0)

Exomes 𝑓: 0.26 ( 2653 hom. )

Failed GnomAD Quality Control

Consequence

APOA2
ENST00000367990.7 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.116

Variant links:

Genes affected

APOA2 (HGNC:601): (apolipoprotein A2) This gene encodes apolipoprotein (apo-) A-II, which is the second most abundant protein of the high density lipoprotein particles. The protein is found in plasma as a monomer, homodimer, or heterodimer with apolipoprotein D. Defects in this gene may result in apolipoprotein A-II deficiency or hypercholesterolemia. [provided by RefSeq, Jul 2008]

APOA2 links:

APOA2 (HGNC:):

APOA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 1-161223055-CCACACA-C is Benign according to our data. Variant chr1-161223055-CCACACA-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 293295.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}. Variant chr1-161223055-CCACACA-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA2	NM_001643.2 linkuse as main transcript	c.53-11_53-6delTGTGTG		splice_region_variant, intron_variant		ENST00000367990.7	NP_001634.1	P02652

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA2	ENST00000367990.7 linkuse as main transcript	c.53-11_53-6delTGTGTG		splice_region_variant, intron_variant		1	NM_001643.2	ENSP00000356969.3		P02652
APOA2	ENST00000470459.6 linkuse as main transcript	c.53-11_53-6delTGTGTG		splice_region_variant, intron_variant		5		ENSP00000477031.1		V9GYS1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

47590

AN:

147306

Hom.:

7589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.282

AC:

55088

AN:

195520

Hom.:

1084

AF XY:

0.283

AC XY:

30133

AN XY:

106664

show subpopulations

Gnomad AFR exome

AF:

0.284

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.349

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.264

AC:

378883

AN:

1435404

Hom.:

2653

AF XY:

0.264

AC XY:

188776

AN XY:

713980

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.272

GnomAD4 genome

AF:

0.323

AC:

47636

AN:

147418

Hom.:

7601

Cov.:

AF XY:

0.327

AC XY:

23426

AN XY:

71626

show subpopulations

Gnomad4 AFR

AF:

0.343

Gnomad4 AMR

AF:

0.338

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.378

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.331

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Apolipoprotein A-II deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Aug 12, 2019

- -

APOA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 28, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over