NM_000081.4(LYST):c.2570C>G (p.Ser857Cys) AND Chédiak-Higashi syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 15, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001206360.10

Allele description [Variation Report for NM_000081.4(LYST):c.2570C>G (p.Ser857Cys)]

NM_000081.4(LYST):c.2570C>G (p.Ser857Cys)

Gene:

LYST:lysosomal trafficking regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.3

Genomic location:

Preferred name:

NM_000081.4(LYST):c.2570C>G (p.Ser857Cys)

HGVS:

NC_000001.11:g.235806566G>C
NG_007397.1:g.82075C>G
NM_000081.4:c.2570C>GMANE SELECT
NM_001301365.1:c.2570C>G
NP_000072.2:p.Ser857Cys
NP_001288294.1:p.Ser857Cys
LRG_143t1:c.2570C>G
LRG_143t2:c.2570C>G
LRG_143:g.82075C>G
LRG_143p2:p.Ser857Cys
NC_000001.10:g.235969866G>C
NM_000081.3:c.2570C>G

Protein change:

S857C

Molecular consequence:

NM_000081.4:c.2570C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001301365.1:c.2570C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Chédiak-Higashi syndrome (CHS)
Synonyms:: Chediak-Higashi Syndrome
Identifiers:: MONDO: MONDO:0008963; MedGen: C0007965; Orphanet: 167; OMIM: 214500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001377666	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21878672, 28492532
SCV003815310	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 26, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001377666

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 15, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003815310

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 26, 2019)

germline

clinical testing

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

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

Subtle differences in CTL cytotoxicity determine susceptibility to hemophagocytic lymphohistiocytosis in mice and humans with Chediak-Higashi syndrome.

Jessen B, Maul-Pavicic A, Ufheil H, Vraetz T, Enders A, Lehmberg K, Längler A, Gross-Wieltsch U, Bay A, Kaya Z, Bryceson YT, Koscielniak E, Badawy S, Davies G, Hufnagel M, Schmitt-Graeff A, Aichele P, Zur Stadt U, Schwarz K, Ehl S.

Blood. 2011 Oct 27;118(17):4620-9. doi: 10.1182/blood-2011-05-356113. Epub 2011 Aug 30.

PubMed [citation]

PMID:: 21878672

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001377666.4

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

Description

This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 857 of the LYST protein (p.Ser857Cys). This variant is present in population databases (rs144261004, gnomAD 0.004%). This missense change has been observed in individual(s) with Chediak-Higashi syndrome (PMID: 21878672). ClinVar contains an entry for this variant (Variation ID: 937365). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain 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

From Revvity Omics, Revvity, SCV003815310.2

#	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

Last Updated: Sep 29, 2024

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