NM_001083116.3(PRF1):c.1153C>T (p.Arg385Trp) AND Familial hemophagocytic lymphohistiocytosis 2

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 26, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000644572.15

Allele description [Variation Report for NM_001083116.3(PRF1):c.1153C>T (p.Arg385Trp)]

NM_001083116.3(PRF1):c.1153C>T (p.Arg385Trp)

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.1153C>T (p.Arg385Trp)

HGVS:

NC_000010.11:g.70598568G>A
NG_009615.1:g.9208C>T
NM_001083116.3:c.1153C>TMANE SELECT
NM_005041.6:c.1153C>T
NP_001076585.1:p.Arg385Trp
NP_005032.2:p.Arg385Trp
LRG_94t1:c.1153C>T
LRG_94:g.9208C>T
NC_000010.10:g.72358324G>A
NM_001083116.1:c.1153C>T

Protein change:

R385W

Links:

dbSNP: rs551046401

NCBI 1000 Genomes Browser:

rs551046401

Molecular consequence:

NM_001083116.3:c.1153C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005041.6:c.1153C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000766272	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 26, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001260922	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (May 25, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27391055, 25215106, 25354579 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000766272

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 26, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001260922

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(May 25, 2017)

germline

clinical testing

PubMed (3)
[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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Decreased function of Fas and variations of the perforin gene in adult patients with primary immune thrombocytopenia.

Boggio E, Gigliotti CL, Rossi D, Toffoletti E, Cappellano G, Clemente N, Puglisi S, Lunghi M, Cerri M, Vianelli N, Cantoni S, Tieghi A, Beggiato E, Gaidano G, Comi C, Chiocchetti A, Fanin R, Dianzani U, Zaja F.

Br J Haematol. 2017 Jan;176(2):258-267. doi: 10.1111/bjh.14248. Epub 2016 Jul 8.

PubMed [citation]

PMID:: 27391055

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000766272.6

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

#	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

From Illumina Laboratory Services, Illumina, SCV001260922.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown 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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