NM_000322.5(PRPH2):c.253G>A (p.Ala85Thr) AND PRPH2-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 17, 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:: RCV001873748.5

Allele description [Variation Report for NM_000322.5(PRPH2):c.253G>A (p.Ala85Thr)]

NM_000322.5(PRPH2):c.253G>A (p.Ala85Thr)

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.253G>A (p.Ala85Thr)

HGVS:

NC_000006.12:g.42722082C>T
NG_009176.2:g.5539G>A
NM_000322.5:c.253G>AMANE SELECT
NP_000313.2:p.Ala85Thr
NC_000006.11:g.42689820C>T
NM_000322.4:c.253G>A

Protein change:

A85T

Links:

dbSNP: rs760311433

NCBI 1000 Genomes Browser:

rs760311433

Molecular consequence:

NM_000322.5:c.253G>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
SCV002151036	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34411390, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002151036

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 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

PRPH2 mutation update: In silico assessment of 245 reported and 7 novel variants in patients with retinal disease.

Peeters MHCA, Khan M, Rooijakkers AAMB, Mulders T, Haer-Wigman L, Boon CJF, Klaver CCW, van den Born LI, Hoyng CB, Cremers FPM, den Hollander AI, Dhaenens CM, Collin RWJ.

Hum Mutat. 2021 Dec;42(12):1521-1547. doi: 10.1002/humu.24275. Epub 2021 Sep 20.

PubMed [citation]

PMID:: 34411390
PMCID:: PMC9290825

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 Invitae, SCV002151036.3

#	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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 85 of the PRPH2 protein (p.Ala85Thr). This variant is present in population databases (rs760311433, gnomAD 0.01%). This missense change has been observed in individual(s) with macular dystrophy (PMID: 34411390). ClinVar contains an entry for this variant (Variation ID: 1175211). 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 not expected to disrupt PRPH2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: May 12, 2024

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