rs2023483

Variant names:

• chr11-17642195-G-C
• rs2023483
• NM_001292063.2:c.8364G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-17642195-G-C
• chr11-17642195-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001292063.2(OTOG):​c.8364G>C​(p.Leu2788Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,548,636 control chromosomes in the GnomAD database, including 81,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10263 hom., cov: 33)
  • Exomes 𝑓: 0.31 (71491 hom.)
• Consequence: OTOG NM_001292063.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -4.72
• Publications: 10 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), 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-17642195-G-C is Benign according to our data. Variant chr11-17642195-G-C is described in ClinVar as Benign. ClinVar VariationId is 226919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	NM_001292063.2	MANE Select	c.8364G>C	p.Leu2788Leu	synonymous	Exon 53 of 56	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.8400G>C	p.Leu2800Leu	synonymous	Exon 52 of 55	NP_001264198.1	Q6ZRI0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	ENST00000399397.6	TSL:5 MANE Select	c.8364G>C	p.Leu2788Leu	synonymous	Exon 53 of 56	ENSP00000382329.2	H9KVB3
	OTOG	ENST00000399391.7	TSL:5	c.8400G>C	p.Leu2800Leu	synonymous	Exon 52 of 55	ENSP00000382323.2	Q6ZRI0-1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53536 AN: 151936 Hom.: 10241 Cov.: 33

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.319

GnomAD2 exomes AF: 0.295 AC: 43244 AN: 146758 AF XY: 0.305

Gnomad AFR exome AF: 0.520

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.191

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.314 AC: 437880 AN: 1396582 Hom.: 71491 Cov.: 37 AF XY: 0.316 AC XY: 217337 AN XY: 688682

African (AFR) AF: 0.521 AC: 16443 AN: 31538

American (AMR) AF: 0.179 AC: 6364 AN: 35584

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6363 AN: 25116

East Asian (EAS) AF: 0.159 AC: 5663 AN: 35692

South Asian (SAS) AF: 0.405 AC: 31980 AN: 78942

European-Finnish (FIN) AF: 0.290 AC: 13948 AN: 48092

Middle Eastern (MID) AF: 0.245 AC: 1397 AN: 5692

European-Non Finnish (NFE) AF: 0.313 AC: 337774 AN: 1078002

Other (OTH) AF: 0.310 AC: 17948 AN: 57924

GnomAD4 genome AF: 0.353 AC: 53605 AN: 152054 Hom.: 10263 Cov.: 33 AF XY: 0.350 AC XY: 26017 AN XY: 74334

African (AFR) AF: 0.507 AC: 21012 AN: 41480

American (AMR) AF: 0.248 AC: 3783 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3464

East Asian (EAS) AF: 0.180 AC: 926 AN: 5158

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4812

European-Finnish (FIN) AF: 0.290 AC: 3077 AN: 10594

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21034 AN: 67950

Other (OTH) AF: 0.320 AC: 677 AN: 2114

Alfa AF: 0.314 Hom.: 1466

Bravo AF: 0.348

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 18B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0060
DANN	Benign	0.64
PhyloP100		-4.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2023483; hg19: chr11-17663742; COSMIC: COSV61130391; COSMIC: COSV61130391;