Submissions for variant NM_000483.5(APOC2):c.229A>C (p.Lys77Gln)

gnomAD frequency: 0.00784  dbSNP: rs5126

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000974450	SCV001122273	benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000991188	SCV001295706	benign	Familial apolipoprotein C-II deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000974450	SCV001814285	likely benign	not provided	2020-11-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31589614, 33111339)
H3Africa Consortium	RCV001777130	SCV002014637	benign	not specified	2020-10-28	criteria provided, single submitter	research	While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.063, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error.
Ambry Genetics	RCV002444415	SCV002734829	benign	Cardiovascular phenotype	2019-08-26	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV000991188	SCV002811419	likely benign	Familial apolipoprotein C-II deficiency	2021-10-23	criteria provided, single submitter	clinical testing
OMIM	RCV000002682	SCV000022840	pathogenic	APOLIPOPROTEIN C-II (AFRICAN)	1986-02-01	no assertion criteria provided	literature only
Reproductive Health Research and Development, BGI Genomics	RCV000991188	SCV001142491	benign	Familial apolipoprotein C-II deficiency	2020-01-06	no assertion criteria provided	curation	NM_000483.4:c.229A>C in the APOC2 gene has an allele frequency of 0.026 in African subpopulation in the gnomAD database, including 8 homozygous occurrences. Pathogenic computational verdict because pathogenic predictions from DANN, MutationAssessor, MutationTaster and SIFTT. aken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2.