rs5122

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_000483.5(APOC2):c.178G>A(p.Glu60Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,613,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E60E) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

APOC2
NM_000483.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1U:1B:3

Conservation

PhyloP100: -3.41

Variant links:

Genes affected

APOC2 (HGNC:609): (apolipoprotein C2) This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is secreted in plasma where it is a component of very low density lipoprotein. This protein activates the enzyme lipoprotein lipase, which hydrolyzes triglycerides and thus provides free fatty acids for cells. Mutations in this gene cause hyperlipoproteinemia type IB, characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. This gene is present in a cluster with other related apolipoprotein genes on chromosome 19. Naturally occurring read-through transcription exists between this gene and the neighboring upstream apolipoprotein C-IV (APOC4) gene. [provided by RefSeq, Mar 2011]

APOC2 links:

APOC4-APOC2 (HGNC:44426): (APOC4-APOC2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring apolipoprotein C-IV (APOC4) and apolipoprotein C-II (APOC2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

APOC4-APOC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05391097).

BP6

Variant 19-44948823-G-A is Benign according to our data. Variant chr19-44948823-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00204 (310/152268) while in subpopulation AFR AF= 0.00715 (297/41544). AF 95% confidence interval is 0.00648. There are 1 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC2	NM_000483.5 link	c.178G>A	p.Glu60Lys	missense_variant	Exon 3 of 4	ENST00000252490.7	NP_000474.2	P02655A0A024R0T9
APOC4-APOC2	NR_037932.1 link	n.1385G>A		non_coding_transcript_exon_variant	Exon 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC2	ENST00000252490.7 link	c.178G>A	p.Glu60Lys	missense_variant	Exon 3 of 4	2	NM_000483.5	ENSP00000252490.5		P02655
APOC4-APOC2	ENST00000589057.5 link	c.409G>A	p.Glu137Lys	missense_variant	Exon 4 of 5	5		ENSP00000468139.1		K7ER74

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00717

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000482

AC:

121

AN:

250930

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.00666

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

267

AN:

1461618

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00636

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00204

AC:

310

AN:

152268

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00715

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000261

Hom.:

Bravo

AF:

0.00227

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000585

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Uncertain:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 18, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 8490626, 31589614, 29100061) -

Oct 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

APOLIPOPROTEIN C-II (SAN FRANCISCO)

Pathogenic:1

Jan 01, 1993

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Familial apolipoprotein C-II deficiency

Uncertain:1

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: curation

NM_000483.4:c.178G>A in the APOC2 gene has an allele frequency of 0.007 in African subpopulation in the gnomAD database. The p.Glu60Lys (NM_000483.4:c.178G>A) was reported as Glu38Lys andd apoc-IIsf in a paper published in 1993 (PMID: 8490626), which is verified by NCBI staff. This variant has been reported in patients with hyperlipidemic. However, functional studies showed no change in enzyme activity to activate lipoprotein lipase; and apoc-IIsf had no difference in the activation energy of the enzyme compared to the normal apoc-II (PubMed: 8490626). Taken together, we interprete this variant as variant of uncertain significance (VUS). ACMG/AMP Criteria applied: BS3; PP4. -

Cardiovascular phenotype

Benign:1

Jul 05, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.022

DANN

Benign

0.61

DEOGEN2

Benign

0.023

T;T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.56

T;T;.;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.054

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L;L;.

PROVEAN

Benign

-1.7

.;N;.;.

REVEL

Benign

0.26

Sift

Benign

0.48

.;T;.;.

Sift4G

Benign

0.69

T;T;T;T

Polyphen

0.0050

.;B;B;.

Vest4

0.69

MVP

0.15

MPC

0.25

ClinPred

0.012

GERP RS

-8.6

Varity_R

0.043

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over