Variant 1-161223055-CCACACACACACACACACACACACA-CCACACACACACACACACACACACACACA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6BS2_Supporting

The NM_001643.2(APOA2):c.53-9_53-6dupTGTG 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 0.0086 ( 10 hom., cov: 0)

Exomes 𝑓: 0.0065 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOA2
NM_001643.2 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 1-161223055-C-CCACA is Benign according to our data. Variant chr1-161223055-C-CCACA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 293293.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=1}.

BS2

High Homozygotes in GnomAd4 at 10 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA2	NM_001643.2 link	c.53-9_53-6dupTGTG		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000367990.7	NP_001634.1	P02652

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA2	ENST00000367990.7 link	c.53-9_53-6dupTGTG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001643.2	ENSP00000356969.3		P02652
APOA2	ENST00000470459.6 link	c.53-9_53-6dupTGTG		splice_region_variant, intron_variant	Intron 2 of 4	5		ENSP00000477031.1		V9GYS1

Frequencies

GnomAD3 genomes

AF:

0.00858

AC:

1266

AN:

147508

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00979

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.00672

Gnomad ASJ

AF:

0.0168

Gnomad EAS

AF:

0.000604

Gnomad SAS

AF:

0.00997

Gnomad FIN

AF:

0.00807

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.00861

Gnomad OTH

AF:

0.00592

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00651

AC:

9344

AN:

1436274

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

4830

AN XY:

714690

show subpopulations

Gnomad4 AFR exome

AF:

0.00659

Gnomad4 AMR exome

AF:

0.00434

Gnomad4 ASJ exome

AF:

0.00992

Gnomad4 EAS exome

AF:

0.000255

Gnomad4 SAS exome

AF:

0.00935

Gnomad4 FIN exome

AF:

0.00581

Gnomad4 NFE exome

AF:

0.00651

Gnomad4 OTH exome

AF:

0.00668

GnomAD4 genome

AF:

0.00857

AC:

1265

AN:

147620

Hom.:

Cov.:

AF XY:

0.00892

AC XY:

640

AN XY:

71724

show subpopulations

Gnomad4 AFR

AF:

0.00979

Gnomad4 AMR

AF:

0.00664

Gnomad4 ASJ

AF:

0.0168

Gnomad4 EAS

AF:

0.000605

Gnomad4 SAS

AF:

0.00998

Gnomad4 FIN

AF:

0.00807

Gnomad4 NFE

AF:

0.00861

Gnomad4 OTH

AF:

0.00586

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apolipoprotein A-II deficiency

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 22, 2021

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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