20-62256189-A-G

Variant names:

• chr20-62256189-A-G
• NM_144498.4:c.5A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144498.4(OSBPL2):​c.5A>G​(p.Asn2Ser) 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. 12/21 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: OSBPL2 NM_144498.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

Genes affected

OSBPL2 (HGNC:15761): (oxysterol binding protein like 2) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain, although the encoded protein contains only the sterol-binding domain. In vitro studies have shown that the encoded protein can bind strongly to phosphatic acid and weakly to phosphatidylinositol 3-phosphate, but cannot bind to 25-hydroxycholesterol. The protein associates with the Golgi apparatus. Transcript variants encoding different isoforms have been described. [provided by RefSeq, Sep 2014]

ACMG classification

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=0.24731916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL2	NM_144498.4	c.5A>G	p.Asn2Ser	missense_variant	Exon 2 of 14	ENST00000313733.9	NP_653081.1
OSBPL2	NM_014835.5	c.5A>G	p.Asn2Ser	missense_variant	Exon 2 of 14		NP_055650.1
OSBPL2	NM_001363878.2	c.-362A>G		5_prime_UTR_variant	Exon 2 of 15		NP_001350807.1
OSBPL2	NM_001278649.3	c.-217A>G		5_prime_UTR_variant	Exon 2 of 13		NP_001265578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9	c.5A>G	p.Asn2Ser	missense_variant	Exon 2 of 14	1	NM_144498.4	ENSP00000316649.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 04, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 2 of the OSBPL2 protein (p.Asn2Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OSBPL2-related conditions. This missense change has been observed in at least one individual who was not affected with OSBPL2-related conditions (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	.;.;T;.;.;T;.;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.77	T;T;.;T;T;.;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;.;M;.;M;M;.;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.11	.;.;N;.;N;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.25	.;.;T;.;T;.;.;.
Sift4G	Benign	0.59	.;T;T;.;T;.;.;.
Polyphen		0.42, 0.56	.;.;B;.;P;B;.;B
Vest4		0.18, 0.19
MutPred		0.39		Gain of phosphorylation at N2 (P = 0.0106);Gain of phosphorylation at N2 (P = 0.0106);Gain of phosphorylation at N2 (P = 0.0106);Gain of phosphorylation at N2 (P = 0.0106);Gain of phosphorylation at N2 (P = 0.0106);Gain of phosphorylation at N2 (P = 0.0106);Gain of phosphorylation at N2 (P = 0.0106);Gain of phosphorylation at N2 (P = 0.0106);
MVP		0.30
MPC		0.48
ClinPred		0.59	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-60831245;