chr1-161223055-CCACACACACACA-C

Variant names:

• chr1-161223055-CCACACACACACA-C
• rs17244502
• NM_001643.2:c.53-17_53-6delTGTGTGTGTGTG

Variant summary

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

The NM_001643.2(APOA2):​c.53-17_53-6delTGTGTGTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,423,886 control chromosomes in the GnomAD database, including 2,403 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1802 hom., cov: 0)
  • Exomes 𝑓: 0.15 (2403 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOA2 NM_001643.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-161223055-CCACACACACACA-C is Benign according to our data. Variant chr1-161223055-CCACACACACACA-C is described in ClinVar as Benign. ClinVar VariationId is 928640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 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.53-17_53-6delTGTGTGTGTGTG		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.53-17_53-6delTGTGTGTGTGTG		splice_region intron	N/A	ENSP00000356969.3	P02652
	APOA2	ENST00000463273.6	TSL:1	c.53-17_53-6delTGTGTGTGTGTG		splice_region intron	N/A	ENSP00000476740.2	P02652
	APOA2	ENST00000470459.6	TSL:5	c.53-17_53-6delTGTGTGTGTGTG		splice_region intron	N/A	ENSP00000477031.1	V9GYS1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22251 AN: 147474 Hom.: 1803 Cov.: 0

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0953

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.177 AC: 34517 AN: 195520 AF XY: 0.172

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.149 AC: 211500 AN: 1423886 Hom.: 2403 AF XY: 0.147 AC XY: 104475 AN XY: 708466

African (AFR) AF: 0.0956 AC: 3159 AN: 33032

American (AMR) AF: 0.227 AC: 9888 AN: 43654

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 4955 AN: 25714

East Asian (EAS) AF: 0.249 AC: 9516 AN: 38176

South Asian (SAS) AF: 0.118 AC: 9904 AN: 83588

European-Finnish (FIN) AF: 0.131 AC: 6235 AN: 47710

Middle Eastern (MID) AF: 0.166 AC: 931 AN: 5622

European-Non Finnish (NFE) AF: 0.145 AC: 157748 AN: 1087426

Other (OTH) AF: 0.155 AC: 9164 AN: 58964

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.151 AC: 22243 AN: 147584 Hom.: 1802 Cov.: 0 AF XY: 0.151 AC XY: 10801 AN XY: 71700

African (AFR) AF: 0.107 AC: 4270 AN: 39946

American (AMR) AF: 0.213 AC: 3168 AN: 14890

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 695 AN: 3402

East Asian (EAS) AF: 0.299 AC: 1482 AN: 4954

South Asian (SAS) AF: 0.118 AC: 542 AN: 4602

European-Finnish (FIN) AF: 0.133 AC: 1323 AN: 9914

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.155 AC: 10297 AN: 66636

Other (OTH) AF: 0.160 AC: 328 AN: 2046

Alfa AF: 0.145 Hom.: 197

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (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;