NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del) AND Familial hemophagocytic lymphohistiocytosis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 11, 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:: RCV001247037.8

Allele description [Variation Report for NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)]

NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)

Gene:

PRF1:perforin 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)

HGVS:

NC_000010.11:g.70598868TCT[3]
NG_009615.1:g.8899AAG[3]
NM_001083116.3:c.844AAG[3]MANE SELECT
NM_005041.6:c.844AAG[3]
NP_001076585.1:p.Lys285del
NP_005032.2:p.Lys285del
LRG_94t1:c.853_855del
LRG_94:g.8899AAG[3]
NC_000010.10:g.72358622_72358624del
NC_000010.10:g.72358624TCT[3]
NM_001083116.1:c.853_855del
NM_001083116.1:c.853_855delAAG
NM_001083116.3:c.853_855delMANE SELECT

Protein change:

K285del

Links:

dbSNP: rs745902829

NCBI 1000 Genomes Browser:

rs745902829

Molecular consequence:

NM_001083116.3:c.844AAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_005041.6:c.844AAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV001420434	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 11, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11179007, 22186995, 25104007, 30539918, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001420434

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 11, 2023)

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

Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis.

Göransdotter Ericson K, Fadeel B, Nilsson-Ardnor S, Söderhäll C, Samuelsson A, Janka G, Schneider M, Gürgey A, Yalman N, Révész T, Egeler R, Jahnukainen K, Storm-Mathiesen I, Haraldsson A, Poole J, de Saint Basile G, Nordenskjöld M, Henter J.

Am J Hum Genet. 2001 Mar;68(3):590-7. Epub 2001 Feb 6.

PubMed [citation]

PMID:: 11179007
PMCID:: PMC1274472

Fatal immune dysregulation due to a gain of glycosylation mutation in lymphocyte perforin.

Chia J, Thia K, Brennan AJ, Little M, Williams B, Lopez JA, Trapani JA, Voskoboinik I.

Blood. 2012 Feb 16;119(7):1713-6. doi: 10.1182/blood-2011-08-374355. Epub 2011 Dec 20.

PubMed [citation]

PMID:: 22186995

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001420434.5

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

Description

This variant, c.853_855del, results in the deletion of 1 amino acid(s) of the PRF1 protein (p.Lys285del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 11179007, 22186995, 25104007, 30539918). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 971288). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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

Last Updated: Sep 29, 2024

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