NM_000322.5(PRPH2):c.454A>G (p.Met152Val) AND PRPH2-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 19, 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:: RCV001050346.9

Allele description [Variation Report for NM_000322.5(PRPH2):c.454A>G (p.Met152Val)]

NM_000322.5(PRPH2):c.454A>G (p.Met152Val)

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.454A>G (p.Met152Val)

HGVS:

NC_000006.12:g.42721881T>C
NG_009176.2:g.5740A>G
NM_000322.5:c.454A>GMANE SELECT
NP_000313.2:p.Met152Val
NC_000006.11:g.42689619T>C
NG_009176.1:g.5740A>G
NM_000322.4:c.454A>G

Protein change:

M152V

Links:

dbSNP: rs146703538

NCBI 1000 Genomes Browser:

rs146703538

Molecular consequence:

NM_000322.5:c.454A>G - 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
SCV001214447	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 19, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31213501, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001214447

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 19, 2023)

germline

clinical testing

PubMed (2)
[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

Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients.

Koyanagi Y, Akiyama M, Nishiguchi KM, Momozawa Y, Kamatani Y, Takata S, Inai C, Iwasaki Y, Kumano M, Murakami Y, Omodaka K, Abe T, Komori S, Gao D, Hirakata T, Kurata K, Hosono K, Ueno S, Hotta Y, Murakami A, Terasaki H, Wada Y, et al.

J Med Genet. 2019 Oct;56(10):662-670. doi: 10.1136/jmedgenet-2018-105691. Epub 2019 Jun 17.

PubMed [citation]

PMID:: 31213501

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, SCV001214447.5

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 152 of the PRPH2 protein (p.Met152Val). This variant is present in population databases (rs146703538, gnomAD 0.02%). This missense change has been observed in individuals with retinitis pigmentosa (PMID: 31213501). ClinVar contains an entry for this variant (Variation ID: 846922). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRPH2 protein function. 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.

#	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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