NM_001083116.3(PRF1):c.1213C>T (p.Gln405Ter) AND Familial hemophagocytic lymphohistiocytosis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 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:: RCV003627048.2

Allele description [Variation Report for NM_001083116.3(PRF1):c.1213C>T (p.Gln405Ter)]

NM_001083116.3(PRF1):c.1213C>T (p.Gln405Ter)

Gene:

PRF1:perforin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_001083116.3(PRF1):c.1213C>T (p.Gln405Ter)

HGVS:

NC_000010.11:g.70598508G>A
NG_009615.1:g.9268C>T
NM_001083116.3:c.1213C>TMANE SELECT
NM_005041.6:c.1213C>T
NP_001076585.1:p.Gln405Ter
NP_001076585.1:p.Gln405Ter
NP_005032.2:p.Gln405Ter
LRG_94t1:c.1213C>T
LRG_94:g.9268C>T
LRG_94p1:p.Gln405Ter
NC_000010.10:g.72358264G>A
NM_001083116.1:c.1213C>T

Protein change:

Q405*

Molecular consequence:

NM_001083116.3:c.1213C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005041.6:c.1213C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Familial hemophagocytic lymphohistiocytosis 2 (FHL2)
Identifiers:: MONDO: MONDO:0011337; MedGen: C1863727; Orphanet: 540; OMIM: 603553

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004384845	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 18, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17477373, 25577959, 33746956, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004384845

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 18, 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

Germline mutations of the perforin gene are a frequent occurrence in childhood anaplastic large cell lymphoma.

Cannella S, Santoro A, Bruno G, Pillon M, Mussolin L, Mangili G, Rosolen A, Aricò M.

Cancer. 2007 Jun 15;109(12):2566-71.

PubMed [citation]

PMID:: 17477373

Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis (FHL) patients in India.

Mhatre S, Madkaikar M, Desai M, Ghosh K.

Blood Cells Mol Dis. 2015 Mar;54(3):250-7. doi: 10.1016/j.bcmd.2014.11.023. Epub 2014 Dec 23.

PubMed [citation]

PMID:: 25577959

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004384845.1

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

Description

This variant has not been reported in the literature in individuals affected with PRF1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gln405*) in the PRF1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 151 amino acid(s) of the PRF1 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PRF1 protein in which other variant(s) (p.Asp491Asn) have been determined to be pathogenic (PMID: 17477373, 25577959, 33746956). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing.

#	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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