NM_005356.5(LCK):c.100G>C (p.Gly34Arg) AND Severe combined immunodeficiency due to LCK deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 10, 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:: RCV002298327.5

Allele description [Variation Report for NM_005356.5(LCK):c.100G>C (p.Gly34Arg)]

NM_005356.5(LCK):c.100G>C (p.Gly34Arg)

Gene:

LCK:LCK proto-oncogene, Src family tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p35.2

Genomic location:

Preferred name:

NM_005356.5(LCK):c.100G>C (p.Gly34Arg)

HGVS:

NC_000001.11:g.32274429G>C
NG_023387.1:g.28191G>C
NM_001042771.3:c.100G>C
NM_001330468.2:c.100G>C
NM_005356.5:c.100G>CMANE SELECT
NP_001036236.1:p.Gly34Arg
NP_001317397.1:p.Gly34Arg
NP_005347.3:p.Gly34Arg
LRG_153t1:c.100G>C
LRG_153:g.28191G>C
LRG_153p1:p.Gly34Arg
NC_000001.10:g.32740030G>C

Protein change:

G34R

Molecular consequence:

NM_001042771.3:c.100G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330468.2:c.100G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005356.5:c.100G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Severe combined immunodeficiency due to LCK deficiency
Synonyms:: Immunodeficiency 22
Identifiers:: MONDO: MONDO:0014334; MedGen: C4014233; Orphanet: 280142; OMIM: 615758

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002597980	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 10, 2023)	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

SCV002597980

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 10, 2023)

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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002597980.3

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

Description

ClinVar contains an entry for this variant (Variation ID: 1720609). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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. This variant has not been reported in the literature in individuals affected with LCK-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 34 of the LCK protein (p.Gly34Arg). This variant is present in population databases (rs770282584, gnomAD 0.0009%).

#	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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