Variant 2-26477904-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_194323.3(OTOF):c.-88A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000971 in 1,534,770 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00077 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00099 ( 22 hom. )

Consequence

OTOF
NM_194323.3 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.137

Variant links:

Genes affected

OTOF (HGNC:8515): (otoferlin) Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has 3 C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has 6 C2 domains. The homology suggests that this protein may be involved in vesicle membrane fusion. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OTOF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-26477904-T-C is Benign according to our data. Variant chr2-26477904-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 179695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOF	NM_194323.3 linkuse as main transcript	c.-88A>G		5_prime_UTR_variant	1/29	ENST00000339598.8	NP_919304.1	Q9HC10-2
OTOF	NM_194248.3 linkuse as main transcript	c.2215-155A>G		intron_variant		ENST00000272371.7	NP_919224.1	Q9HC10-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOF	ENST00000339598.8 linkuse as main transcript	c.-88A>G		5_prime_UTR_variant	1/29	1	NM_194323.3	ENSP00000344521.3		Q9HC10-2
OTOF	ENST00000272371.7 linkuse as main transcript	c.2215-155A>G		intron_variant		1	NM_194248.3	ENSP00000272371.2		Q9HC10-1

Frequencies

GnomAD3 genomes

AF:

0.000776

AC:

118

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00206

AC:

299

AN:

145334

Hom.:

AF XY:

0.00263

AC XY:

202

AN XY:

76688

show subpopulations

Gnomad AFR exome

AF:

0.000383

Gnomad AMR exome

AF:

0.000527

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000450

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.000994

AC:

1374

AN:

1382672

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

908

AN XY:

680176

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.000650

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000257

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.000769

AC:

117

AN:

152098

Hom.:

Cov.:

AF XY:

0.000996

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0112

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000755

Hom.:

Bravo

AF:

0.000487

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 30, 2015

c.-11A>G in intron 1A of OTOF: This variant is not expected to have clinical sig nificance because it has been identified in 1.4% (76/5536) of South Asian chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs143933877). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

6.0

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over