NM_030882.4:c.988A>C

Variant names:

• chr22-36227430-T-G
• rs200674632
• NM_030882.4:c.988A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_030882.4(APOL2):​c.988A>C​(p.Met330Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,606,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: APOL2 NM_030882.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.10
• Publications: 0 publications found

Genes affected

APOL2 (HGNC:619): (apolipoprotein L2) This gene is a member of the apolipoprotein L gene family. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids or allow the binding of lipids to organelles. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

APOL2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.061690718).
• BS2: High AC in GnomAd4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030882.4. 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
	APOL2	NM_030882.4	MANE Select	c.988A>C	p.Met330Leu	missense	Exon 5 of 5	NP_112092.2	Q9BQE5
	APOL2	NM_145637.3		c.988A>C	p.Met330Leu	missense	Exon 6 of 6	NP_663612.2	Q9BQE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL2	ENST00000358502.10	TSL:1 MANE Select	c.988A>C	p.Met330Leu	missense	Exon 5 of 5	ENSP00000351292.5	Q9BQE5
	APOL2	ENST00000249066.10	TSL:1	c.988A>C	p.Met330Leu	missense	Exon 6 of 6	ENSP00000249066.6	Q9BQE5
	APOL2	ENST00000451256.6	TSL:2	c.1324A>C	p.Met442Leu	missense	Exon 6 of 6	ENSP00000403153.2	J3KQL8

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 16 AN: 151416 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000920

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: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000776 AC: 19 AN: 244888 AF XY: 0.0000754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.000105

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000633

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.0000344 AC: 50 AN: 1455210 Hom.: 0 Cov.: 35 AF XY: 0.0000304 AC XY: 22 AN XY: 723734

African (AFR) AF: 0.0000299 AC: 1 AN: 33406

American (AMR) AF: 0.000247 AC: 11 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25590

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53054

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.0000307 AC: 34 AN: 1107840

Other (OTH) AF: 0.0000499 AC: 3 AN: 60072

GnomAD4 genome AF: 0.000106 AC: 16 AN: 151532 Hom.: 0 Cov.: 33 AF XY: 0.000162 AC XY: 12 AN XY: 74084

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.000919 AC: 14 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67818

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000455 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.014
DANN	Benign	0.32
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.019
Sift	Benign	0.65	T
Sift4G	Benign	0.66	T
Vest4		0.066
MutPred		0.48		Loss of MoRF binding (P = 0.1625)
MVP		0.13
MPC		0.064
ClinPred		0.022	T
GERP RS		1.0
gMVP		0.044
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200674632; hg19: chr22-36623476;