NM_206933.4(USH2A):c.12332C>T (p.Ser4111Phe) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 2024
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:: RCV001241616.7

Allele description [Variation Report for NM_206933.4(USH2A):c.12332C>T (p.Ser4111Phe)]

NM_206933.4(USH2A):c.12332C>T (p.Ser4111Phe)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.12332C>T (p.Ser4111Phe)

HGVS:

NC_000001.11:g.215675579G>A
NG_009497.2:g.752870C>T
NM_206933.4:c.12332C>TMANE SELECT
NP_996816.3:p.Ser4111Phe
NC_000001.10:g.215848921G>A
NG_009497.1:g.752818C>T
NM_206933.2:c.12332C>T
NM_206933.3:c.12332C>T
c.12332C>T

Protein change:

S4111F

Links:

dbSNP: rs142095945

NCBI 1000 Genomes Browser:

rs142095945

Molecular consequence:

NM_206933.4:c.12332C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001414646	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30902645, 32037395, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001414646

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2024)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genomic Landscape of Sporadic Retinitis Pigmentosa: Findings from 877 Spanish Cases.

Martin-Merida I, Avila-Fernandez A, Del Pozo-Valero M, Blanco-Kelly F, Zurita O, Perez-Carro R, Aguilera-Garcia D, Riveiro-Alvarez R, Arteche A, Trujillo-Tiebas MJ, Tahsin-Swafiri S, Rodriguez-Pinilla E, Lorda-Sanchez I, Garcia-Sandoval B, Corton M, Ayuso C.

Ophthalmology. 2019 Aug;126(8):1181-1188. doi: 10.1016/j.ophtha.2019.03.018. Epub 2019 Mar 20.

PubMed [citation]

PMID:: 30902645

Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations.

Zampaglione E, Kinde B, Place EM, Navarro-Gomez D, Maher M, Jamshidi F, Nassiri S, Mazzone JA, Finn C, Schlegel D, Comander J, Pierce EA, Bujakowska KM.

Genet Med. 2020 Jun;22(6):1079-1087. doi: 10.1038/s41436-020-0759-8. Epub 2020 Feb 10.

PubMed [citation]

PMID:: 32037395
PMCID:: PMC7272325

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001414646.5

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

Description

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 4111 of the USH2A protein (p.Ser4111Phe). This variant is present in population databases (rs142095945, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of USH2A-related conditions ‚Äã (PMID: 30902645, 32037395; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 48396). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt USH2A protein function with a negative predictive value of 95%. 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

Last Updated: Apr 7, 2025

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