20-62260002-C-T

Variant names:

• chr20-62260002-C-T
• NM_144498.4:c.59C>T

Variant summary

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

The NM_001363878.2(OSBPL2):​c.-308C>T variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL2 NM_001363878.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

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=0.06703937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL2	NM_144498.4	c.59C>T	p.Ser20Phe	missense_variant	Exon 3 of 14	ENST00000313733.9	NP_653081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL2	ENST00000313733.9	c.59C>T	p.Ser20Phe	missense_variant	Exon 3 of 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

Jul 23, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.68
DEOGEN2	Benign	0.072	.;.;T;.;T;.;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.75	T;D;.;D;.;D;D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.067	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;.;M;.;M;.;M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.32	.;.;N;.;.;.;.
REVEL	Benign	0.032
Sift	Benign	0.71	.;.;T;.;.;.;.
Sift4G	Uncertain	0.044	.;D;T;.;.;.;.
Polyphen		0.073	.;.;B;.;B;.;B
Vest4		0.28
MutPred		0.21		Loss of glycosylation at S20 (P = 0.0123);Loss of glycosylation at S20 (P = 0.0123);Loss of glycosylation at S20 (P = 0.0123);Loss of glycosylation at S20 (P = 0.0123);Loss of glycosylation at S20 (P = 0.0123);Loss of glycosylation at S20 (P = 0.0123);Loss of glycosylation at S20 (P = 0.0123);
MVP		0.15
MPC		1.3
ClinPred		0.67	D
GERP RS		2.8
Varity_R		0.039
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: chr20-60835058;