NM_007074.4(CORO1A):c.595C>T (p.Arg199Cys) AND Severe combined immunodeficiency due to CORO1A deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 13, 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:: RCV001201428.8

Allele description [Variation Report for NM_007074.4(CORO1A):c.595C>T (p.Arg199Cys)]

NM_007074.4(CORO1A):c.595C>T (p.Arg199Cys)

Genes:

LOC121587541:Sharpr-MPRA regulatory region 7413 [Gene]
CORO1A:coronin 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_007074.4(CORO1A):c.595C>T (p.Arg199Cys)

HGVS:

NC_000016.10:g.30187182C>T
NG_023415.1:g.8578C>T
NM_001193333.3:c.595C>T
NM_007074.4:c.595C>TMANE SELECT
NP_001180262.1:p.Arg199Cys
NP_009005.1:p.Arg199Cys
LRG_195:g.8578C>T
NC_000016.9:g.30198503C>T
NM_007074.3:c.595C>T

Protein change:

R199C

Links:

dbSNP: rs763170903

NCBI 1000 Genomes Browser:

rs763170903

Molecular consequence:

NM_001193333.3:c.595C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_007074.4:c.595C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Severe combined immunodeficiency due to CORO1A deficiency
Synonyms:: Immunodeficiency 8; IMMUNODEFICIENCY 8 WITH LYMPHOPROLIFERATION
Identifiers:: MONDO: MONDO:0014168; MedGen: C3809383; Orphanet: 228003; OMIM: 615401

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001372495	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002783729	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 7, 2022)	unknown	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

SCV001372495

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2022)

germline

clinical testing

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

SCV002783729

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 7, 2022)

unknown

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
not provided	unknown	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001372495.4

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 199 of the CORO1A protein (p.Arg199Cys). This variant is present in population databases (rs763170903, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CORO1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 933253). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 Fulgent Genetics, Fulgent Genetics, SCV002783729.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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