NM_206933.4(USH2A):c.12295-2A>G AND not provided

Clinical significance:Pathogenic (Last evaluated: May 5, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001057968.4

Allele description [Variation Report for NM_206933.4(USH2A):c.12295-2A>G]

NM_206933.4(USH2A):c.12295-2A>G

Gene:
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.12295-2A>G
HGVS:
  • NC_000001.11:g.215675618T>C
  • NG_009497.1:g.752779A>G
  • NG_009497.2:g.752831A>G
  • NM_206933.4:c.12295-2A>GMANE SELECT
  • NC_000001.10:g.215848960T>C
  • NM_206933.2:c.12295-2A>G
  • c.12295-2A>G
Links:
dbSNP: rs151148854
NCBI 1000 Genomes Browser:
rs151148854
Molecular consequence:
  • NM_206933.4:c.12295-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001222499Invitaecriteria provided, single submitter
Pathogenic
(Aug 20, 2020)
germlineclinical testing

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

SCV001777205GeneDxcriteria provided, single submitter
Pathogenic
(May 5, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

High-throughput sequencing for the molecular diagnosis of Usher syndrome reveals 42 novel mutations and consolidates CEP250 as Usher-like disease causative.

Fuster-García C, García-García G, Jaijo T, Fornés N, Ayuso C, Fernández-Burriel M, Sánchez-De la Morena A, Aller E, Millán JM.

Sci Rep. 2018 Nov 20;8(1):17113. doi: 10.1038/s41598-018-35085-0.

PubMed [citation]
PMID:
30459346
PMCID:
PMC6244211

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
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001222499.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change affects an acceptor splice site in intron 62 of the USH2A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of Usher syndrome (PMID: 30459346, Invitae). ClinVar contains an entry for this variant (Variation ID: 48392). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). For these reasons, this variant has been classified as Pathogenic.

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

From GeneDx, SCV001777205.1

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

Description

Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar as pathogenic or likely pathogenic but additional evidence is not available (SCV000065410.5, SCV000795417.1; Landrum et al., 2016); Has not been previously published as pathogenic or benign to our knowledge

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

Last Updated: Nov 27, 2021

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