NM_001292063.2:c.4162_4179delAAGCCCTCGGGGGCTGCC

Variant names:

• chr11-17608296-ATGCCAAGCCCTCGGGGGC-A
• rs876657940
• NM_001292063.2:c.4162_4179delAAGCCCTCGGGGGCTGCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001292063.2(OTOG):​c.4162_4179delAAGCCCTCGGGGGCTGCC​(p.Lys1388_Ala1393del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OTOG NM_001292063.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

Genes affected

OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

OTOG Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 18B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001292063.2.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	NM_001292063.2	MANE Select	c.4162_4179delAAGCCCTCGGGGGCTGCC	p.Lys1388_Ala1393del	conservative_inframe_deletion	Exon 34 of 56	NP_001278992.1
	OTOG	NM_001277269.2		c.4198_4215delAAGCCCTCGGGGGCTGCC	p.Lys1400_Ala1405del	conservative_inframe_deletion	Exon 33 of 55	NP_001264198.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	ENST00000399397.6	TSL:5 MANE Select	c.4162_4179delAAGCCCTCGGGGGCTGCC	p.Lys1388_Ala1393del	conservative_inframe_deletion	Exon 34 of 56	ENSP00000382329.2
	OTOG	ENST00000399391.7	TSL:5	c.4198_4215delAAGCCCTCGGGGGCTGCC	p.Lys1400_Ala1405del	conservative_inframe_deletion	Exon 33 of 55	ENSP00000382323.2
	OTOG	ENST00000342528.2	TSL:2	n.1500_1517delAAGCCCTCGGGGGCTGCC		non_coding_transcript_exon	Exon 10 of 22

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

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

Other links and lift over

dbSNP: rs876657940; hg19: chr11-17629843;