NM_006445.4(PRPF8):c.6956_6957dup (p.Leu2320fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 24, 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:: RCV003568324.2

Allele description [Variation Report for NM_006445.4(PRPF8):c.6956_6957dup (p.Leu2320fs)]

NM_006445.4(PRPF8):c.6956_6957dup (p.Leu2320fs)

Gene:

PRPF8:pre-mRNA processing factor 8 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17p13.3

Genomic location:

Preferred name:

NM_006445.4(PRPF8):c.6956_6957dup (p.Leu2320fs)

HGVS:

NC_000017.11:g.1650854AG[3]
NG_009118.1:g.39027TC[3]
NG_033061.1:g.4243TC[3]
NM_006445.4:c.6956_6957dupMANE SELECT
NP_006436.3:p.Leu2320fs
NC_000017.10:g.1554146_1554147insGA
NC_000017.10:g.1554148AG[3]

Protein change:

L2320fs

Molecular consequence:

NM_006445.4:c.6956_6957dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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PREDICTED: Oryzias latipes HEAT repeat containing 3 (heatr3), transcript variant...
PREDICTED: Oryzias latipes HEAT repeat containing 3 (heatr3), transcript variant X2, mRNA
gi|1343945740|ref|XM_011493677.3|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004306562	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 24, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20232351, 21378395, 28515276, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004306562

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 24, 2023)

germline

clinical testing

PubMed (4)
[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

Prognosis for splicing factor PRPF8 retinitis pigmentosa, novel mutations and correlation between human and yeast phenotypes.

Towns KV, Kipioti A, Long V, McKibbin M, Maubaret C, Vaclavik V, Ehsani P, Springell K, Kamal M, Ramesar RS, Mackey DA, Moore AT, Mukhopadhyay R, Webster AR, Black GC, O'Sullivan J, Bhattacharya SS, Pierce EA, Beggs JD, Inglehearn CF.

Hum Mutat. 2010 May;31(5):E1361-76. doi: 10.1002/humu.21236.

PubMed [citation]

PMID:: 20232351

PRPF mutations are associated with generalized defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa.

Tanackovic G, Ransijn A, Thibault P, Abou Elela S, Klinck R, Berson EL, Chabot B, Rivolta C.

Hum Mol Genet. 2011 Jun 1;20(11):2116-30. doi: 10.1093/hmg/ddr094. Epub 2011 Mar 5.

PubMed [citation]

PMID:: 21378395
PMCID:: PMC3090192

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004306562.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PRPF8 protein in which other variant(s) (p.Tyr2334Asn) have been determined to be pathogenic (PMID: 20232351, 21378395, 28515276; 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with PRPF8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the PRPF8 gene (p.Leu2320Serfs*40). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the PRPF8 protein and extend the protein by 23 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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