NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter) AND Familial hemophagocytic lymphohistiocytosis 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 16, 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:: RCV002933279.2

Allele description [Variation Report for NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter)]

NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter)

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.449C>A (p.Ser150Ter)

HGVS:

NC_000010.11:g.70600454G>T
NG_009615.1:g.7322C>A
NM_001083116.3:c.449C>AMANE SELECT
NM_005041.6:c.449C>A
NP_001076585.1:p.Ser150Ter
NP_001076585.1:p.Ser150Ter
NP_005032.2:p.Ser150Ter
LRG_94t1:c.449C>A
LRG_94:g.7322C>A
LRG_94p1:p.Ser150Ter
NC_000010.10:g.72360210G>T
NM_001083116.1:c.449C>A

Protein change:

S150*

Molecular consequence:

NM_001083116.3:c.449C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_005041.6:c.449C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003265800	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 14757862, 1156555, 16860143, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003265800

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 16, 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

Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis.

Molleran Lee S, Villanueva J, Sumegi J, Zhang K, Kogawa K, Davis J, Filipovich AH.

J Med Genet. 2004 Feb;41(2):137-44. No abstract available.

PubMed [citation]

PMID:: 14757862
PMCID:: PMC1735659

Emotions and skin (II)-the conditioning of scratch responses in cases of lichen simplex.

Roberston IM, Jordan JM, Whitlock FA.

Br J Dermatol. 1975 Apr;92(4):407-12.

PubMed [citation]

PMID:: 1156555

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003265800.2

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2055336). This variant is also known as S150X. This premature translational stop signal has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 14757862). This variant is present in population databases (rs773267292, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Ser150*) in the PRF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRF1 are known to be pathogenic (PMID: 1156555, 16860143).

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine