NM_000322.5(PRPH2):c.518A>C (p.Asp173Ala) AND PRPH2-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 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:: RCV001379736.7

Allele description [Variation Report for NM_000322.5(PRPH2):c.518A>C (p.Asp173Ala)]

NM_000322.5(PRPH2):c.518A>C (p.Asp173Ala)

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.518A>C (p.Asp173Ala)

HGVS:

NC_000006.12:g.42721817T>G
NG_009176.2:g.5804A>C
NM_000322.5:c.518A>CMANE SELECT
NP_000313.2:p.Asp173Ala
NC_000006.11:g.42689555T>G
NG_009176.1:g.5804A>C
NM_000322.4:c.518A>C

Protein change:

D173A

Links:

dbSNP: rs61755794

NCBI 1000 Genomes Browser:

rs61755794

Molecular consequence:

NM_000322.5:c.518A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001577585	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31456290, 8019570, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001577585

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2023)

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

A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).

Sharon D, Ben-Yosef T, Goldenberg-Cohen N, Pras E, Gradstein L, Soudry S, Mezer E, Zur D, Abbasi AH, Zeitz C, Cremers FPM, Khan MI, Levy J, Rotenstreich Y, Birk OS, Ehrenberg M, Leibu R, Newman H, Shomron N, Banin E, Perlman I.

Hum Mutat. 2020 Jan;41(1):140-149. doi: 10.1002/humu.23903. Epub 2019 Sep 15.

PubMed [citation]

PMID:: 31456290

Mutations in the human peripherin/RDS gene associated with autosomal dominant retinitis pigmentosa.

Grüning G, Millan JM, Meins M, Beneyto M, Caballero M, Apfelstedt-Sylla E, Bosch R, Zrenner E, Prieto F, Gal A.

Hum Mutat. 1994;3(3):321-3. No abstract available.

PubMed [citation]

PMID:: 8019570

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001577585.4

#	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 aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 173 of the PRPH2 protein (p.Asp173Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant inherited retinal dystrophy (PMID: 31456290; Invitae). ClinVar contains an entry for this variant (Variation ID: 812387). 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 variant disrupts the p.Asp173 amino acid residue in PRPH2. Other variant(s) that disrupt this residue have been observed in individuals with PRPH2-related conditions (PMID: 8019570), which suggests that this may be a clinically significant amino acid residue. 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: Sep 29, 2024

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