Genetic Variant APOA2:c.53-21_53-6dupTGTGTGTGTGTGTGTG (chr1-161223055-C-CCACACACACACACACA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001643.2(APOA2):c.53-21_53-6dupTGTGTGTGTGTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APOA2
NM_001643.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.116

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

apolipoprotein A-II amyloidosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

APOA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001643.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA2	NM_001643.2	MANE Select	c.53-21_53-6dupTGTGTGTGTGTGTGTG		splice_region intron	N/A	NP_001634.1	P02652

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOA2	ENST00000367990.7	TSL:1 MANE Select	c.53-21_53-6dupTGTGTGTGTGTGTGTG	splice_region intron	N/A	ENSP00000356969.3	P02652
APOA2	ENST00000463273.6	TSL:1	c.53-21_53-6dupTGTGTGTGTGTGTGTG	splice_region intron	N/A	ENSP00000476740.2	P02652
APOA2	ENST00000470459.6	TSL:5	c.53-21_53-6dupTGTGTGTGTGTGTGTG	splice_region intron	N/A	ENSP00000477031.1	V9GYS1

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

147528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000502

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: AS_VQSR

AF:

0.00000555

AC:

AN:

1440770

Hom.:

Cov.:

AF XY:

0.00000977

AC XY:

AN XY:

716838

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33098

American (AMR)

AF:

0.00

AC:

AN:

44032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25778

East Asian (EAS)

AF:

0.00

AC:

AN:

39172

South Asian (SAS)

AF:

0.0000937

AC:

AN:

85396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100024

Other (OTH)

AF:

0.00

AC:

AN:

59576

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000451525), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.344

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000136

AC:

AN:

147528

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71606

show subpopulations

African (AFR)

AF:

0.0000502

AC:

AN:

39842

American (AMR)

AF:

0.00

AC:

AN:

14882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

4968

South Asian (SAS)

AF:

0.00

AC:

AN:

4614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66654

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.12

Splicing

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

Publications

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1-161223055-CCACACACACACACACACACACACA-CCACACACACACACACACACACACACACACACACACACACA

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