NM_000322.5(PRPH2):c.964_965del (p.Ser322fs) AND PRPH2-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 29, 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:: RCV002554769.3

Allele description [Variation Report for NM_000322.5(PRPH2):c.964_965del (p.Ser322fs)]

NM_000322.5(PRPH2):c.964_965del (p.Ser322fs)

Gene:

PRPH2:peripherin 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_000322.5(PRPH2):c.964_965del (p.Ser322fs)

HGVS:

NC_000006.12:g.42698372TC[1]
NC_000006.12:g.42698372_42698373TC[1]
NG_009176.2:g.29247AG[1]
NM_000322.5:c.964_965delMANE SELECT
NP_000313.2:p.Ser322fs
NC_000006.11:g.42666109_42666110del
NC_000006.11:g.42666110TC[1]
NM_000322.4:c.964_965del

Protein change:

S322fs

Links:

dbSNP: rs1799985749

NCBI 1000 Genomes Browser:

rs1799985749

Molecular consequence:

NM_000322.5:c.964_965del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003239999	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 29, 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

SCV003239999

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 29, 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, SCV003239999.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PRPH2 protein in which other variant(s) (p.Val332Glu) have been determined to be pathogenic (PMID: 30718709, 32531846; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 867132). This variant has not been reported in the literature in individuals affected with PRPH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the PRPH2 gene (p.Ser322Cysfs*69). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the PRPH2 protein and extend the protein by 43 additional amino acid residues.

#	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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