chr1-161223055-CCACACACACA-C

Variant names:

• chr1-161223055-CCACACACACA-C
• rs17244502
• NM_001643.2:c.53-15_53-6delTGTGTGTGTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001643.2(APOA2):​c.53-15_53-6delTGTGTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,434,990 control chromosomes in the GnomAD database, including 1,176 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (992 hom., cov: 0)
  • Exomes 𝑓: 0.13 (1176 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOA2 NM_001643.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:4
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-161223055-CCACACACACA-C is Benign according to our data. Variant chr1-161223055-CCACACACACA-C is described in ClinVar as Benign. ClinVar VariationId is 929172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

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.53-15_53-6delTGTGTGTGTG		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.53-15_53-6delTGTGTGTGTG		splice_region intron	N/A	ENSP00000356969.3	P02652
	APOA2	ENST00000463273.6	TSL:1	c.53-15_53-6delTGTGTGTGTG		splice_region intron	N/A	ENSP00000476740.2	P02652
	APOA2	ENST00000470459.6	TSL:5	c.53-15_53-6delTGTGTGTGTG		splice_region intron	N/A	ENSP00000477031.1	V9GYS1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16037 AN: 147468 Hom.: 988 Cov.: 0

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.135 AC: 26380 AN: 195520 AF XY: 0.137

Gnomad AFR exome AF: 0.0565

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.0585

Gnomad EAS exome AF: 0.181

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.127 AC: 182324 AN: 1434990 Hom.: 1176 AF XY: 0.127 AC XY: 90994 AN XY: 713994

African (AFR) AF: 0.0486 AC: 1599 AN: 32922

American (AMR) AF: 0.114 AC: 4977 AN: 43750

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 1474 AN: 25664

East Asian (EAS) AF: 0.188 AC: 7318 AN: 38832

South Asian (SAS) AF: 0.158 AC: 13434 AN: 85110

European-Finnish (FIN) AF: 0.114 AC: 5459 AN: 47786

Middle Eastern (MID) AF: 0.0906 AC: 509 AN: 5616

European-Non Finnish (NFE) AF: 0.128 AC: 140302 AN: 1096034

Other (OTH) AF: 0.122 AC: 7252 AN: 59276

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.109 AC: 16052 AN: 147580 Hom.: 992 Cov.: 0 AF XY: 0.109 AC XY: 7847 AN XY: 71700

African (AFR) AF: 0.0518 AC: 2071 AN: 39958

American (AMR) AF: 0.106 AC: 1584 AN: 14892

Ashkenazi Jewish (ASJ) AF: 0.0570 AC: 194 AN: 3402

East Asian (EAS) AF: 0.170 AC: 843 AN: 4958

South Asian (SAS) AF: 0.179 AC: 825 AN: 4604

European-Finnish (FIN) AF: 0.113 AC: 1116 AN: 9914

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.135 AC: 9021 AN: 66616

Other (OTH) AF: 0.106 AC: 218 AN: 2048

Alfa AF: 0.107 Hom.: 197

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	APOA2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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;