1-161222461-G-T

Variant names:

• chr1-161222461-G-T
• rs5088
• NM_001643.2:c.247C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001643.2(APOA2):​c.247C>A​(p.Leu83Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L83Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: APOA2 NM_001643.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA2	NM_001643.2	c.247C>A	p.Leu83Met	missense_variant	Exon 4 of 4	ENST00000367990.7	NP_001634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA2	ENST00000367990.7	c.247C>A	p.Leu83Met	missense_variant	Exon 4 of 4	1	NM_001643.2	ENSP00000356969.3
APOA2	ENST00000470459.6	c.201-8C>A		splice_region_variant, intron_variant	Intron 4 of 4	5		ENSP00000477031.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;T;T;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.63	T;.;T;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.0	N;.;.;.;.
REVEL	Benign	0.24
Sift	Uncertain	0.014	D;.;.;.;.
Sift4G	Uncertain	0.046	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.28
MutPred		0.84		Gain of methylation at K78 (P = 0.098);.;.;.;Gain of methylation at K78 (P = 0.098);
MVP		0.15
MPC		0.90
ClinPred		0.26	T
GERP RS		1.9
Varity_R		0.10
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 12

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

Publications

LitVar

Other links and lift over

dbSNP: rs5088; hg19: chr1-161192251;