20-62260067-A-C

Position:

• chr20-62260067-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144498.4(OSBPL2):​c.124A>C​(p.Asn42His) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL2 NM_144498.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.576

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052835345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL2	NM_144498.4	c.124A>C	p.Asn42His	missense_variant	3/14	ENST00000313733.9	NP_653081.1
OSBPL2	NM_014835.5	c.88A>C	p.Asn30His	missense_variant	3/14		NP_055650.1
OSBPL2	NM_001363878.2	c.-243A>C		5_prime_UTR_variant	3/15		NP_001350807.1
OSBPL2	NM_001278649.3	c.-184-3549A>C		intron_variant			NP_001265578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9	c.124A>C	p.Asn42His	missense_variant	3/14	1	NM_144498.4	ENSP00000316649.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 19, 2022

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. This variant has not been reported in the literature in individuals affected with OSBPL2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 42 of the OSBPL2 protein (p.Asn42His). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.4
DANN	Benign	0.80
DEOGEN2	Benign	0.019	.;T;.;.;T;.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.48	T;.;T;T;.;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.053	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;.;.;L;.;.;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.080	.;N;.;N;.;.;.;.
REVEL	Benign	0.019
Sift	Benign	0.61	.;T;.;T;.;.;.;.
Sift4G	Benign	0.14	T;T;.;T;.;.;.;.
Polyphen		0.0	.;B;.;B;B;.;.;B
Vest4		0.20, 0.21
MutPred		0.41		Loss of stability (P = 0.0798);Loss of stability (P = 0.0798);Loss of stability (P = 0.0798);.;Loss of stability (P = 0.0798);.;Loss of stability (P = 0.0798);Loss of stability (P = 0.0798);
MVP		0.13
MPC		0.61
ClinPred		0.038	T
GERP RS		-1.1
Varity_R		0.023
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr20-60835123;