1-161223055-CCACACACACACACACACACACACA-CCACACACA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

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. 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 id is 3046168.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA2	NM_001643.2	c.53-21_53-6delTGTGTGTGTGTGTGTG		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000367990.7	NP_001634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA2	ENST00000367990.7	c.53-21_53-6delTGTGTGTGTGTGTGTG		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001643.2	ENSP00000356969.3
APOA2	ENST00000470459.6	c.53-21_53-6delTGTGTGTGTGTGTGTG		splice_region_variant, intron_variant	Intron 2 of 4	5		ENSP00000477031.1

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

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.000227

Gnomad4 ASJ exome AF: 0.000233

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00396

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.000218

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

Gnomad4 AFR AF: 0.0000251

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000294

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00625

Gnomad4 NFE AF: 0.000225

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

APOA2-related disorder Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17244502; hg19: chr1-161192845;