NM_030882.4:c.617T>C

Variant names:

• chr22-36227801-A-G
• NM_030882.4:c.617T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030882.4(APOL2):​c.617T>C​(p.Val206Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: APOL2 NM_030882.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08441013).

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.617T>C	p.Val206Ala	missense	Exon 5 of 5	NP_112092.2	Q9BQE5
	APOL2	NM_145637.3		c.617T>C	p.Val206Ala	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.617T>C	p.Val206Ala	missense	Exon 5 of 5	ENSP00000351292.5	Q9BQE5
	APOL2	ENST00000249066.10	TSL:1	c.617T>C	p.Val206Ala	missense	Exon 6 of 6	ENSP00000249066.6	Q9BQE5
	APOL2	ENST00000451256.6	TSL:2	c.953T>C	p.Val318Ala	missense	Exon 6 of 6	ENSP00000403153.2	J3KQL8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

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	0.28
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.1
DANN	Benign	0.60
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.060
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.079
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Vest4		0.023
MutPred		0.68		Loss of stability (P = 0.0512)
MVP		0.076
MPC		0.078
ClinPred		0.16	T
GERP RS		-0.69
gMVP		0.17
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

hg19: chr22-36623847;