chr11-77180404-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000260.4(MYO7A):c.2617C>T(p.Arg873Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00116 in 1,611,950 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R873Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.2617C>T | p.Arg873Trp | missense_variant | 22/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.2617C>T | p.Arg873Trp | missense_variant | 22/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000841 AC: 128AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00102 AC: 251AN: 245898Hom.: 1 AF XY: 0.00115 AC XY: 154AN XY: 134040
GnomAD4 exome AF: 0.00119 AC: 1743AN: 1459682Hom.: 1 Cov.: 32 AF XY: 0.00117 AC XY: 852AN XY: 725980
GnomAD4 genome ? AF: 0.000841 AC: 128AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.000900 AC XY: 67AN XY: 74446
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 16, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 03, 2022 | Identified in the heterozygous state in individuals with Usher syndrome or hearing loss as well as unaffected members of some families, and no second pathogenic variant was reported in the affected individuals (Kothiyal et al., 2010; Vastinsalo et al., 2013; Zazo Seco et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22135276, 21487335, 23891399, 20146813, 30245029, 34426522, 28000701, 22681893, 34391192) - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Autosomal dominant nonsyndromic hearing loss 11 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Dec 20, 2018 | This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Usher syndrome type 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Nov 03, 2021 | NM_000260.3(MYO7A):c.2617C>T(R873W) is a missense variant classified as a variant of uncertain significance in the context of MYO7A-related disorders. R873W has been observed in cases with relevant disease (PMID: 22681893, 20146813, 28000701). Functional assessments of this variant are not available in the literature. R873W has been observed in population frequency databases (gnomAD: FIN 0.23%). In summary, there is insufficient evidence to classify NM_000260.3(MYO7A):c.2617C>T(R873W) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. - |
Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Meniere disease Uncertain:1
Uncertain significance, criteria provided, single submitter | case-control | Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO) | Dec 14, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 09, 2012 | p.Arg873Trp in exon 22 of MYO7A: This variant has been reported in 4 individual s with sensorineural hearing loss or Usher syndrome; however, none of these indi viduals had a second MYO7A variant (Saihan 2011, Kothiyal 2010, Strike 2008). Th is variant has also been identified in 0.2% (141/62260) of European chromosomes including 1 homozygote by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs200454015). Based upon identification in 0.2% of contr ols and not identifying a second MYO7A variant in any affected individuals, this variant is likely benign. - |
Usher syndrome type 1B Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at