NM_206933.4(USH2A):c.486-14G>A AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jul 1, 2024
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:: RCV000414183.37

Allele description [Variation Report for NM_206933.4(USH2A):c.486-14G>A]

NM_206933.4(USH2A):c.486-14G>A

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.486-14G>A

HGVS:

NC_000001.11:g.216418693C>T
NG_009497.2:g.9756G>A
NM_007123.6:c.486-14G>A
NM_206933.4:c.486-14G>AMANE SELECT
NC_000001.10:g.216592035C>T
NG_009497.1:g.9704G>A
NM_206933.2:c.486-14G>A
NM_206933.3:c.486-14G>A

Links:

dbSNP: rs374536346

NCBI 1000 Genomes Browser:

rs374536346

Molecular consequence:

NM_007123.6:c.486-14G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_206933.4:c.486-14G>A - intron variant - [Sequence Ontology: SO:0001627]

Observations:

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
SCV000490866	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Sep 28, 2023)	germline	clinical testing	Citation Link,
SCV001236140	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 1, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22334370, 27957503, 20052763, 28492532
SCV001961166	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Sep 1, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490866

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Sep 28, 2023)

germline

clinical testing

Citation Link,

SCV001236140

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 1, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001961166

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Sep 1, 2021)

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	2	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

Next-generation genetic testing for retinitis pigmentosa.

Neveling K, Collin RW, Gilissen C, van Huet RA, Visser L, Kwint MP, Gijsen SJ, Zonneveld MN, Wieskamp N, de Ligt J, Siemiatkowska AM, Hoefsloot LH, Buckley MF, Kellner U, Branham KE, den Hollander AI, Hoischen A, Hoyng C, Klevering BJ, van den Born LI, Veltman JA, Cremers FP, et al.

Hum Mutat. 2012 Jun;33(6):963-72. doi: 10.1002/humu.22045. Epub 2012 Mar 19. Erratum in: Hum Mutat. 2013 Aug;34(8):1181.

PubMed [citation]

PMID:: 22334370
PMCID:: PMC3490376

Usher syndrome in Denmark: mutation spectrum and some clinical observations.

Dad S, Rendtorff ND, Tranebjærg L, Grønskov K, Karstensen HG, Brox V, Nilssen Ø, Roux AF, Rosenberg T, Jensen H, Møller LB.

Mol Genet Genomic Med. 2016 Sep;4(5):527-539.

PubMed [citation]

PMID:: 27957503
PMCID:: PMC5023938

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000490866.3

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

Description

Published functional studies suggest a damaging effect on gene splicing (Le Guedard-Mereuze et al., 2010); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 31589614, 28944237, 20052763, 27957503, 25078356, 22334370, 24944099, 31964843)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001236140.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change falls in intron 2 of the USH2A gene. It does not directly change the encoded amino acid sequence of the USH2A protein. This variant is present in population databases (rs374536346, gnomAD 0.009%). This variant has been observed in individual(s) with retinitis pigmentosa and/or Usher syndrome (PMID: 22334370, 27957503). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372543). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20052763). 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 CeGaT Center for Human Genetics Tuebingen, SCV001961166.28

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	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		2	not provided	not provided	not provided

Last Updated: Oct 25, 2025

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