22-36227901-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000358502.10(APOL2):​c.517A>G​(p.Asn173Asp) 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. 14/19 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
ENST00000358502.10 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0300
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09866741).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APOL2NM_030882.4 linkuse as main transcriptc.517A>G p.Asn173Asp missense_variant 5/5 ENST00000358502.10 NP_112092.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APOL2ENST00000358502.10 linkuse as main transcriptc.517A>G p.Asn173Asp missense_variant 5/51 NM_030882.4 ENSP00000351292 P2
APOL2ENST00000249066.10 linkuse as main transcriptc.517A>G p.Asn173Asp missense_variant 6/61 ENSP00000249066 P2
APOL2ENST00000451256.6 linkuse as main transcriptc.853A>G p.Asn285Asp missense_variant 6/62 ENSP00000403153 A2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2023The c.517A>G (p.N173D) alteration is located in exon 6 (coding exon 3) of the APOL2 gene. This alteration results from a A to G substitution at nucleotide position 517, causing the asparagine (N) at amino acid position 173 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.1
DANN
Benign
0.93
DEOGEN2
Benign
0.067
.;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.37
.;T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.099
T;T;T
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.020
Sift
Benign
0.38
T;T;T
Sift4G
Benign
0.61
T;T;T
Vest4
0.043
MutPred
0.45
Loss of MoRF binding (P = 0.0403);Loss of MoRF binding (P = 0.0403);.;
MVP
0.21
MPC
0.074
ClinPred
0.046
T
GERP RS
0.042
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
gMVP
0.26

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs555460579; hg19: chr22-36623947; API