NM_000322.5(PRPH2):c.995T>A (p.Val332Glu) AND PRPH2-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 10, 2022
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:: RCV001248001.7

Allele description [Variation Report for NM_000322.5(PRPH2):c.995T>A (p.Val332Glu)]

NM_000322.5(PRPH2):c.995T>A (p.Val332Glu)

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.995T>A (p.Val332Glu)

HGVS:

NC_000006.12:g.42698341A>T
NG_009176.2:g.29280T>A
NM_000322.5:c.995T>AMANE SELECT
NP_000313.2:p.Val332Glu
NC_000006.11:g.42666079A>T
NG_009176.1:g.29280T>A
NM_000322.4:c.995T>A

Protein change:

V332E

Links:

dbSNP: rs1582759492

NCBI 1000 Genomes Browser:

rs1582759492

Molecular consequence:

NM_000322.5:c.995T>A - 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
SCV001421460	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 10, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30718709, 32531846, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001421460

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 10, 2022)

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

Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.

Jespersgaard C, Fang M, Bertelsen M, Dang X, Jensen H, Chen Y, Bech N, Dai L, Rosenberg T, Zhang J, Møller LB, Tümer Z, Brøndum-Nielsen K, Grønskov K.

Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.

PubMed [citation]

PMID:: 30718709
PMCID:: PMC6362094

Genotype-phenotype associations in a large PRPH2-related retinopathy cohort.

Reeves MJ, Goetz KE, Guan B, Ullah E, Blain D, Zein WM, Tumminia SJ, Hufnagel RB.

Hum Mutat. 2020 Sep;41(9):1528-1539. doi: 10.1002/humu.24065. Epub 2020 Jul 5.

PubMed [citation]

PMID:: 32531846
PMCID:: PMC7484419

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001421460.5

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

Description

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. ClinVar contains an entry for this variant (Variation ID: 636192). This missense change has been observed in individuals with clinical features of autosomal dominant PRPH2-related conditions (PMID: 30718709, 32531846; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 332 of the PRPH2 protein (p.Val332Glu).

#	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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