rs786205881

chr20-62260083-CTG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_144498.4(OSBPL2):c.141_142del(p.Arg50AlafsTer103) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL2 NM_144498.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.21

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_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 20-62260083-CTG-C is Pathogenic according to our data. Variant chr20-62260083-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 190111.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr20-62260083-CTG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSBPL2	NM_144498.4	c.141_142del	p.Arg50AlafsTer103	frameshift_variant	3/14	ENST00000313733.9
OSBPL2	NM_014835.5	c.105_106del	p.Arg38AlafsTer103	frameshift_variant	3/14
OSBPL2	NM_001363878.2	c.-226_-225del		5_prime_UTR_variant	3/15
OSBPL2	NM_001278649.3	c.-184-3532_-184-3531del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSBPL2	ENST00000313733.9	c.141_142del	p.Arg50AlafsTer103	frameshift_variant	3/14	1	NM_144498.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 67 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 10, 2015

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs786205881; hg19: chr20-60835139;