NM_000260.4(MYO7A):c.1344-2A>G AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 25, 2023
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:: RCV001852738.6

Allele description [Variation Report for NM_000260.4(MYO7A):c.1344-2A>G]

NM_000260.4(MYO7A):c.1344-2A>G

Gene:

MYO7A:myosin VIIA [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.5

Genomic location:

Preferred name:

NM_000260.4(MYO7A):c.1344-2A>G

HGVS:

NC_000011.10:g.77162118A>G
NG_009086.2:g.38873A>G
NM_000260.4:c.1344-2A>GMANE SELECT
NM_001127180.2:c.1344-2A>G
NM_001369365.1:c.1311-2A>G
LRG_1420t1:c.1344-2A>G
LRG_1420:g.38873A>G
NC_000011.9:g.76873164A>G
NM_000260.3:c.1344-2A>G
c.1344-2A>G

Links:

dbSNP: rs111033415

NCBI 1000 Genomes Browser:

rs111033415

Molecular consequence:

NM_000260.4:c.1344-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001127180.2:c.1344-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001369365.1:c.1311-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236652	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 25, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16199547, 8900236, 25404053, 15823922, 26445815, 27460420, 28492532
SCV002526468	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 17, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236652

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 25, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002526468

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 17, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients.

Weston MD, Kelley PM, Overbeck LD, Wagenaar M, Orten DJ, Hasson T, Chen ZY, Corey D, Mooseker M, Sumegi J, Cremers C, Moller C, Jacobson SG, Gorin MB, Kimberling WJ.

Am J Hum Genet. 1996 Nov;59(5):1074-83.

PubMed [citation]

PMID:: 8900236
PMCID:: PMC1914835

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV002236652.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change affects an acceptor splice site in intron 12 of the MYO7A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with autosomal recessive deafness and/or autosomal recessive Usher syndrome (PMID: 15823922, 26445815, 27460420). This variant is also known as c.1244-2A>G. ClinVar contains an entry for this variant (Variation ID: 43143). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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		not provided	not provided	not provided	not provided

From GeneDx, SCV002526468.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15823922, 31479088)

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

Last Updated: Jul 15, 2024

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