NM_001083116.3(PRF1):c.808_812del (p.Gly270fs) AND Familial hemophagocytic lymphohistiocytosis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 2021
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:: RCV001949278.4

Allele description [Variation Report for NM_001083116.3(PRF1):c.808_812del (p.Gly270fs)]

NM_001083116.3(PRF1):c.808_812del (p.Gly270fs)

Gene:

PRF1:perforin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_001083116.3(PRF1):c.808_812del (p.Gly270fs)

HGVS:

NC_000010.11:g.70598909_70598913del
NG_009615.1:g.8863_8867del
NM_001083116.3:c.808_812delMANE SELECT
NM_005041.6:c.808_812del
NP_001076585.1:p.Gly270fs
NP_005032.2:p.Gly270fs
LRG_94:g.8863_8867del
NC_000010.10:g.72358665_72358669del

Protein change:

G270fs

Links:

dbSNP: rs2132476381

NCBI 1000 Genomes Browser:

rs2132476381

Molecular consequence:

NM_001083116.3:c.808_812del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005041.6:c.808_812del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Mycena chlorophus, Mycena indigotica, Mycena kentingensis, Mycena sanguinolenta ...
Mycena chlorophus, Mycena indigotica, Mycena kentingensis, Mycena sanguinolenta and Mycena venus
Mycena genome sequencing and assembly

BioProject
Elovl5 ELOVL fatty acid elongase 5 [Mus musculus]
Elovl5 ELOVL fatty acid elongase 5 [Mus musculus]
Gene ID:68801

Gene
68801[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002247151	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17601962, 21152410, 29357941, 27290639, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247151

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2021)

germline

clinical testing

PubMed (5)
[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

Cytophagic histiocytic panniculitis with fatal haemophagocytic lymphohistiocytosis in a paediatric patient with perforin gene mutation.

Chen RL, Hsu YH, Ueda I, Imashuku S, Takeuchi K, Tu BP, Chuang SS.

J Clin Pathol. 2007 Oct;60(10):1168-9. Epub 2007 Jun 29. No abstract available.

PubMed [citation]

PMID:: 17601962
PMCID:: PMC2014859

Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes.

Nagai K, Yamamoto K, Fujiwara H, An J, Ochi T, Suemori K, Yasumi T, Tauchi H, Koh K, Sato M, Morimoto A, Heike T, Ishii E, Yasukawa M.

PLoS One. 2010 Nov 30;5(11):e14173. doi: 10.1371/journal.pone.0014173.

PubMed [citation]

PMID:: 21152410
PMCID:: PMC2994802

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002247151.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). 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.Arg390*) have been determined to be pathogenic (PMID: 17601962, 21152410, 29357941; 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. This premature translational stop signal has been observed in individual(s) with suspected mitochondrial disorder (PMID: 27290639). This sequence change creates a premature translational stop signal (p.Gly270Hisfs*9) in the PRF1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 286 amino acid(s) of the PRF1 protein.

#	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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