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NM_016239.4(MYO15A):c.7547C>T (p.Ala2516Val) AND Autosomal recessive nonsyndromic hearing loss 3

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
May 22, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001002758.6

Allele description [Variation Report for NM_016239.4(MYO15A):c.7547C>T (p.Ala2516Val)]

NM_016239.4(MYO15A):c.7547C>T (p.Ala2516Val)

Gene:
MYO15A:myosin XVA [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_016239.4(MYO15A):c.7547C>T (p.Ala2516Val)
HGVS:
  • NC_000017.11:g.18151183C>T
  • NG_011634.2:g.47478C>T
  • NM_016239.4:c.7547C>TMANE SELECT
  • NP_057323.3:p.Ala2516Val
  • NC_000017.10:g.18054497C>T
  • NG_011634.1:g.47478C>T
  • NM_016239.3:c.7547C>T
Protein change:
A2516V
Links:
dbSNP: rs201073816
NCBI 1000 Genomes Browser:
rs201073816
Molecular consequence:
  • NM_016239.4:c.7547C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 3
Synonyms:
NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 3; Deafness, autosomal recessive 3
Identifiers:
MONDO: MONDO:0010860; MedGen: C1838263; Orphanet: 90636; OMIM: 600316

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000401183Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)
Uncertain significance
(Jan 13, 2018)
germlineclinical testing

Citation Link,

SCV000992401Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital
criteria provided, single submitter

(ClinGen HL ACMG Specifications v1)
Uncertain significancematernalcase-control

PubMed (1)
[See all records that cite this PMID]

SCV0025215523billion
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(May 22, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedmaternalunknown21not providednot providedyescase-control
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss.

Oza AM, DiStefano MT, Hemphill SE, Cushman BJ, Grant AR, Siegert RK, Shen J, Chapin A, Boczek NJ, Schimmenti LA, Murry JB, Hasadsri L, Nara K, Kenna M, Booth KT, Azaiez H, Griffith A, Avraham KB, Kremer H, Rehm HL, Amr SS, Abou Tayoun AN; et al.

Hum Mutat. 2018 Nov;39(11):1593-1613. doi: 10.1002/humu.23630.

PubMed [citation]
PMID:
30311386
PMCID:
PMC6188673

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000401183.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, SCV000992401.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providedyescase-control PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalunknownnot providednot providednot provided2not provided1not provided

From 3billion, SCV002521552.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.018%). In silico tool predictions suggest no damaging effect of the variant on gene or gene product (REVEL: 0.17; 3Cnet: 0.00). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024