20-62259751-GGCACTGGAGCTCGCTGGGA-GGCACTGGAGCTCGCTGGGAGCACTGGAGCTCGCTGGGA

Variant names:

• chr20-62259751-G-GGCACTGGAGCTCGCTGGGA
• rs3215942
• NM_144498.4:c.38-227_38-209dupACTGGAGCTCGCTGGGAGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_144498.4(OSBPL2):​c.38-227_38-209dupACTGGAGCTCGCTGGGAGC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: OSBPL2 NM_144498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• Publications: 0 publications found

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]

OSBPL2 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 67

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144498.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL2	NM_144498.4	MANE Select	c.38-227_38-209dupACTGGAGCTCGCTGGGAGC		intron	N/A	NP_653081.1	Q9H1P3-1
	OSBPL2	NM_014835.5		c.38-263_38-245dupACTGGAGCTCGCTGGGAGC		intron	N/A	NP_055650.1	Q9H1P3-2
	OSBPL2	NM_001363878.2		c.-329-227_-329-209dupACTGGAGCTCGCTGGGAGC		intron	N/A	NP_001350807.1	A0A2R8YDU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL2	ENST00000313733.9	TSL:1 MANE Select	c.38-230_38-229insGCACTGGAGCTCGCTGGGA		intron	N/A	ENSP00000316649.3	Q9H1P3-1
	OSBPL2	ENST00000358053.3	TSL:1	c.38-266_38-265insGCACTGGAGCTCGCTGGGA		intron	N/A	ENSP00000350755.2	Q9H1P3-2
	OSBPL2	ENST00000865094.1		c.38-230_38-229insGCACTGGAGCTCGCTGGGA		intron	N/A	ENSP00000535153.1

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3215942; hg19: chr20-60834807;