1-161223055-CCACACACACACACACACACACACA-CCACACACA

Variant names:

• chr1-161223055-CCACACACACACACACA-C
• rs17244502
• NM_001643.2:c.53-21_53-6delTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6 BS2_Supporting

The NM_001643.2(APOA2):​c.53-21_53-6delTGTGTGTGTGTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,587,612 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. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00054 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: APOA2 NM_001643.2 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.506
• Publications: 4 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 1-161223055-CCACACACACACACACA-C is Benign according to our data. Variant chr1-161223055-CCACACACACACACACA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3046168.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 79 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.53-21_53-6delTGTGTGTGTGTGTGTG		splice_region intron	N/A	NP_001634.1	P02652

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.000536 AC: 79 AN: 147522 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00625

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000225

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000250 AC: 360 AN: 1440090 Hom.: 0 AF XY: 0.000261 AC XY: 187 AN XY: 716518

African (AFR) AF: 0.0000302 AC: 1 AN: 33096

American (AMR) AF: 0.000227 AC: 10 AN: 43992

Ashkenazi Jewish (ASJ) AF: 0.000233 AC: 6 AN: 25750

East Asian (EAS) AF: 0.000128 AC: 5 AN: 39104

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85388

European-Finnish (FIN) AF: 0.00396 AC: 190 AN: 48034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.000121 AC: 133 AN: 1099544

Other (OTH) AF: 0.000218 AC: 13 AN: 59542

GnomAD4 genome AF: 0.000536 AC: 79 AN: 147522 Hom.: 1 Cov.: 0 AF XY: 0.000852 AC XY: 61 AN XY: 71604

African (AFR) AF: 0.0000251 AC: 1 AN: 39842

American (AMR) AF: 0.00 AC: 0 AN: 14880

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 4968

South Asian (SAS) AF: 0.00 AC: 0 AN: 4614

European-Finnish (FIN) AF: 0.00625 AC: 62 AN: 9920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000225 AC: 15 AN: 66652

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 197

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	APOA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs17244502; hg19: chr1-161192845;