NM_000311.5(PRNP):c.222_245del (p.60PHGGGWGQ[3]) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 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:: RCV003388076.1

Allele description [Variation Report for NM_000311.5(PRNP):c.222_245del (p.60PHGGGWGQ[3])]

NM_000311.5(PRNP):c.222_245del (p.60PHGGGWGQ[3])

Gene:

PRNP:prion protein (Kanno blood group) [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20p13

Genomic location:

Preferred name:

NM_000311.5(PRNP):c.222_245del (p.60PHGGGWGQ[3])

HGVS:

NC_000020.11:g.4699442_4699465del
NG_009087.1:g.18292_18315del
NM_000311.3:c.222_245del24
NM_000311.5:c.222_245delMANE SELECT
NM_001080121.3:c.222_245del
NM_001080122.3:c.222_245del
NM_001080123.3:c.222_245del
NM_001271561.3:c.133_156del
NM_183079.4:c.222_245del
NP_000302.1:p.60PHGGGWGQ[3]
NP_001073590.1:p.60PHGGGWGQ[3]
NP_001073591.1:p.60PHGGGWGQ[3]
NP_001073592.1:p.60PHGGGWGQ[3]
NP_001258490.1:p.Ala45_Gly52del
NP_898902.1:p.60PHGGGWGQ[3]
NC_000020.10:g.4680071_4680094del
NC_000020.10:g.4680088_4680111del

Links:

dbSNP: rs754362804

NCBI 1000 Genomes Browser:

rs754362804

Molecular consequence:

NM_000311.5:c.222_245del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001080121.3:c.222_245del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001080122.3:c.222_245del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001080123.3:c.222_245del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001271561.3:c.133_156del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_183079.4:c.222_245del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004099939	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Sep 18, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16914329, 35812092, 22717776, 18455951 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004099939

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Sep 18, 2023)

germline

clinical testing

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

Citation Link

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

High frequency occurrence of 1-OPRD variant of PRNP gene in gastric cancer cell lines and Chinese population with gastric cancer.

Liang J, Wang JB, Pan YL, Wang J, Liu LL, Guo XY, Sun L, Lin T, Han S, Xie HH, Yin F, Guo XG, Fan D.

Cell Biol Int. 2006 Nov;30(11):920-3. Epub 2006 Jul 7.

PubMed [citation]

PMID:: 16914329

Case Report: Genetic Creutzfeldt-Jakob Disease With a G114V Mutation and One Octapeptide Repeat Deletion as a Mimic of Frontotemporal Dementia.

Lin X, Xu Y, Zhen Z, Xiao K, Chen X, Yang J, Guan H, Shi Q, Dong X, Wang J, Guo Y.

Front Neurol. 2022;13:888309. doi: 10.3389/fneur.2022.888309.

PubMed [citation]

PMID:: 35812092
PMCID:: PMC9263511

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004099939.1

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

Description

Variant summary: PRNP c.222_245del24 (p.Pro84_Gln91del) results in an in-frame deletion that is predicted to remove eight amino acids from the encoded protein. The variant allele was found at a frequency of 8.6e-05 in 245424 control chromosomes. It is observed and reported as a polymorphic Octapeptide Repeat Deletion (ORPD) in the general population. This frequency does not allow conclusions about variant significance. c.222_245del24 has been reported in the literature with other co-occurring variants on uncertain significance and/or as a polymorphic repeat in individuals affected with Dementia, Insomnia, Parkinson Disease and gastric cancer cell lines (example, Lin_2022, Luo_2012, Wang_2009, Liang_2006). These report(s) do not provide unequivocal conclusions about association of the variant with PRNP-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 35812092, 22717776, 18455951, 16914329). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: Sep 29, 2024

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