NM_000322.5(PRPH2):c.419A>G (p.Tyr140Cys) AND PRPH2-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 8, 2023
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:: RCV001894157.4

Allele description [Variation Report for NM_000322.5(PRPH2):c.419A>G (p.Tyr140Cys)]

NM_000322.5(PRPH2):c.419A>G (p.Tyr140Cys)

Gene:

PRPH2:peripherin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_000322.5(PRPH2):c.419A>G (p.Tyr140Cys)

HGVS:

NC_000006.12:g.42721916T>C
NG_009176.2:g.5705A>G
NM_000322.5:c.419A>GMANE SELECT
NP_000313.2:p.Tyr140Cys
NC_000006.11:g.42689654T>C

Protein change:

Y140C

Links:

dbSNP: rs1761910060

NCBI 1000 Genomes Browser:

rs1761910060

Molecular consequence:

NM_000322.5:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PRPH2-related disorder
Synonyms:: PRPH2-Related Disorders; PRPH2-related condition
Identifiers:: MedGen: CN239395

Recent activity

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protein TALPID3 isoform X14 [Homo sapiens]
protein TALPID3 isoform X14 [Homo sapiens]
gi|2217299137|ref|XP_047287966.1|

Protein
Incest
Incest
Sexual intercourse between persons so closely related that they are forbidden by law to marry.<br/>Year introduced: 1967

MeSH
High-Frequency Jet Ventilation
High-Frequency Jet Ventilation
Respiratory support system used primarily with rates of about 100 to 200/min with volumes of from about one to three times predicted anatomic dead space. Used to treat respira...<br/>Year introduced: 1988

MeSH
Brachial Plexus Neuritis
Brachial Plexus Neuritis
A syndrome associated with inflammation of the BRACHIAL PLEXUS. Clinical features include severe pain in the shoulder region which may be accompanied by MUSCLE WEAKNESS and lo...<br/>Year introduced: 2000

MeSH
Myocardial Revascularization
Myocardial Revascularization
The restoration of blood supply to the myocardium. (From Dorland, 28th ed)<br/>Year introduced: 1973

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002127373	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002127373

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 8, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002127373.3

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

Description

ClinVar contains an entry for this variant (Variation ID: 1358170). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PRPH2 protein function. This missense change has been observed in individuals with clinical features of autosomal dominant inherited retinal dystrophy and/or Stargardt disease (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 140 of the PRPH2 protein (p.Tyr140Cys).

#	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: Oct 26, 2024

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