NM_016239.4(MYO15A):c.8050T>C (p.Tyr2684His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 13, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000607828.5

Allele description [Variation Report for NM_016239.4(MYO15A):c.8050T>C (p.Tyr2684His)]

NM_016239.4(MYO15A):c.8050T>C (p.Tyr2684His)

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.8050T>C (p.Tyr2684His)

HGVS:

NC_000017.11:g.18153858T>C
NG_011634.2:g.50153T>C
NM_016239.4:c.8050T>CMANE SELECT
NP_057323.3:p.Tyr2684His
NC_000017.10:g.18057172T>C
NG_011634.1:g.50153T>C
NM_016239.3:c.8050T>C

Protein change:

Y2684H

Links:

dbSNP: rs376351191

NCBI 1000 Genomes Browser:

rs376351191

Molecular consequence:

NM_016239.4:c.8050T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000711137	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Sep 13, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26633542, 29986705, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000711137

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Sep 13, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	3	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical application of whole-exome sequencing across clinical indications.

Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, Vertino-Bell A, Smaoui N, Neidich J, Monaghan KG, McKnight D, Bai R, Suchy S, Friedman B, Tahiliani J, Pineda-Alvarez D, Richard G, Brandt T, Haverfield E, Chung WK, Bale S.

Genet Med. 2016 Jul;18(7):696-704. doi: 10.1038/gim.2015.148. Epub 2015 Dec 3.

PubMed [citation]

PMID:: 26633542

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.

Cabanillas R, Diñeiro M, Cifuentes GA, Castillo D, Pruneda PC, Álvarez R, Sánchez-Durán N, Capín R, Plasencia A, Viejo-Díaz M, García-González N, Hernando I, Llorente JL, Repáraz-Andrade A, Torreira-Banzas C, Rosell J, Govea N, Gómez-Martínez JR, Núñez-Batalla F, Garrote JA, Mazón-Gutiérrez Á, Costales M, et al.

BMC Med Genomics. 2018 Jul 9;11(1):58. doi: 10.1186/s12920-018-0375-5.

PubMed [citation]

PMID:: 29986705
PMCID:: PMC6038346

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000711137.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Tyr2684His variant in MYO15A has been previously reported in at least 3 individuals with hearing loss, one individual was compound heterozygous for a second likely pathogenic MYO15A, and one individual harbored a rare variant of uncertain significance that was confirmed in trans (Cabanillas 2018, Retterer 2015, Santos Serrao de Castro, 2012, LMM unpublished data). The variant has segregated in an affected sibling (Santos Serrao de Castro, 2012). This variant was identified in 0.07% (8/10344) of Ashkenazi Jewish chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Tyr2684His variant is uncertain. ACMG/AMP criteria applied: PM3, PP1, PP3.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		3	not provided	2	not provided

Last Updated: May 16, 2025

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