NM_006445.4(PRPF8):c.6991del (p.Glu2331fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001221596.7

Allele description

NM_006445.4(PRPF8):c.6991del (p.Glu2331fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

17p13.3

Genomic location:

Preferred name:

NM_006445.4(PRPF8):c.6991del (p.Glu2331fs)

HGVS:

NC_000017.11:g.1650821del
NG_009118.1:g.39064del
NG_033061.1:g.4280del
NM_006445.4:c.6991delMANE SELECT
NP_006436.3:p.Glu2331fs
NC_000017.10:g.1554113del
NC_000017.10:g.1554115del
NM_006445.3:c.6991del

Protein change:

E2331fs

Links:

dbSNP: rs1910994795

NCBI 1000 Genomes Browser:

rs1910994795

Molecular consequence:

NM_006445.4:c.6991del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Aphyocypris arcus strain cyp892 early growth response 1 (EGR1) gene, partial cds
Aphyocypris arcus strain cyp892 early growth response 1 (EGR1) gene, partial cds
gi|973690925|gb|KP694470.1|

Nucleotide
Aphyocypris arcus strain cyp892 recombination activating protein 1 (RAG1) gene, ...
Aphyocypris arcus strain cyp892 recombination activating protein 1 (RAG1) gene, partial cds
gi|973693399|gb|KP695707.1|

Nucleotide
insulin-like growth factor 2 mRNA-binding protein 1 isoform X2 [Homo sapiens]
insulin-like growth factor 2 mRNA-binding protein 1 isoform X2 [Homo sapiens]
gi|2462552427|ref|XP_054170703.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001393652	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8571961, 16799052, 20232351, 28492532
SCV002525425	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Apr 28, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001393652

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 27, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002525425

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Apr 28, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa.

Kojis TL, Heinzmann C, Flodman P, Ngo JT, Sparkes RS, Spence MA, Bateman JB, Heckenlively JR.

Am J Hum Genet. 1996 Feb;58(2):347-55.

PubMed [citation]

PMID:: 8571961
PMCID:: PMC1914553

Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families.

Sullivan LS, Bowne SJ, Birch DG, Hughbanks-Wheaton D, Heckenlively JR, Lewis RA, Garcia CA, Ruiz RS, Blanton SH, Northrup H, Gire AI, Seaman R, Duzkale H, Spellicy CJ, Zhu J, Shankar SP, Daiger SP.

Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3052-64.

PubMed [citation]

PMID:: 16799052
PMCID:: PMC2585061

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001393652.4

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

Description

This sequence change results in a frameshift in the PRPF8 gene (p.Glu2331Argfs*28). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the PRPF8 protein and extend the protein by 22 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 8571961, 16799052, 20232351). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 949989). For these reasons, this variant has been classified as 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

From GeneDx, SCV002525425.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation as the last 5 amino acids are lost and replaced with 27 incorrect amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Not observed in large population cohorts (gnomAD); Located in the critical region required for interaction with EFTUD2 and SNRNP200 (Pena et al., 2007; Mozaffari-Jovin et al., 2013).; This variant is associated with the following publications: (PMID: 20232351, 31049658, 16799052, 29087248, 8571961, 17317632, 23704370)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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