Genetic Variant APOA2:c.53-23_53-6delTGTGTGTGTGTGTGTGTG (chr1-161223055-CCACACACACACACACACA-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001643.2(APOA2):c.53-23_53-6delTGTGTGTGTGTGTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000659 in 1,588,402 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.00051 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00067 ( 1 hom. )

Consequence

APOA2
NM_001643.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.506

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS2

High AC in GnomAd4 at 75 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.53-23_53-6delTGTGTGTGTGTGTGTGTG		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.53-23_53-6delTGTGTGTGTGTGTGTGTG	splice_region intron	N/A	ENSP00000356969.3	P02652
APOA2	ENST00000463273.6	TSL:1	c.53-23_53-6delTGTGTGTGTGTGTGTGTG	splice_region intron	N/A	ENSP00000476740.2	P02652
APOA2	ENST00000470459.6	TSL:5	c.53-23_53-6delTGTGTGTGTGTGTGTGTG	splice_region intron	N/A	ENSP00000477031.1	V9GYS1

Frequencies

GnomAD3 genomes

AF:

0.000508

AC:

AN:

147528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000753

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

Gnomad ASJ

AF:

0.00412

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000605

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.000986

GnomAD4 exome

AF:

0.000674

AC:

971

AN:

1440762

Hom.:

AF XY:

0.000600

AC XY:

430

AN XY:

716838

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

33098

American (AMR)

AF:

0.0000227

AC:

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.00376

AC:

AN:

25776

East Asian (EAS)

AF:

0.00

AC:

AN:

39170

South Asian (SAS)

AF:

0.00

AC:

AN:

85402

European-Finnish (FIN)

AF:

0.000791

AC:

AN:

48050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.000713

AC:

784

AN:

1100018

Other (OTH)

AF:

0.000789

AC:

AN:

59576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

144

192

240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000508

AC:

AN:

147640

Hom.:

Cov.:

AF XY:

0.000488

AC XY:

AN XY:

71730

show subpopulations

African (AFR)

AF:

0.0000751

AC:

AN:

39960

American (AMR)

AF:

0.000134

AC:

AN:

14902

Ashkenazi Jewish (ASJ)

AF:

0.00412

AC:

AN:

3402

East Asian (EAS)

AF:

0.00

AC:

AN:

4958

South Asian (SAS)

AF:

0.00

AC:

AN:

4608

European-Finnish (FIN)

AF:

0.000605

AC:

AN:

9922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

66646

Other (OTH)

AF:

0.000977

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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1-161223055-CCACACACACACACACACACACACA-CCACACA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over