NM_001083116.3(PRF1):c.1620A>G (p.Gln540=) AND Familial hemophagocytic lymphohistiocytosis 2

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 31, 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:: RCV000887811.17

Allele description [Variation Report for NM_001083116.3(PRF1):c.1620A>G (p.Gln540=)]

NM_001083116.3(PRF1):c.1620A>G (p.Gln540=)

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.1620A>G (p.Gln540=)

HGVS:

NC_000010.11:g.70598101T>C
NG_009615.1:g.9675A>G
NM_001083116.3:c.1620A>GMANE SELECT
NM_005041.6:c.1620A>G
NP_001076585.1:p.Gln540=
NP_005032.2:p.Gln540=
LRG_94t1:c.1620A>G
LRG_94:g.9675A>G
NC_000010.10:g.72357857T>C
NM_001083116.1:c.1620A>G
NM_005041.4:c.1620A>G

Links:

dbSNP: rs149776121

NCBI 1000 Genomes Browser:

rs149776121

Molecular consequence:

NM_001083116.3:c.1620A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_005041.6:c.1620A>G - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV001031397	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001260918	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18496551, 15077010 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001031397

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 31, 2024)

germline

clinical testing

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

SCV001260918

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

PubMed (2)
[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

Variations of the perforin gene in patients with multiple sclerosis.

Cappellano G, Orilieri E, Comi C, Chiocchetti A, Bocca S, Boggio E, Bernardone IS, Cometa A, Clementi R, Barizzone N, D'Alfonso S, Corrado L, Galimberti D, Scarpini E, Guerini FR, Caputo D, Paolicelli D, Trojano M, Figà-Talamanca L, Salvetti M, Perla F, Leone M, et al.

Genes Immun. 2008 Jul;9(5):438-44. doi: 10.1038/gene.2008.35. Epub 2008 May 22.

PubMed [citation]

PMID:: 18496551

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001031397.6

#	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, SCV001260918.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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: Oct 20, 2024

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