NM_000246.4(CIITA):c.566C>T (p.Ala189Val) AND MHC class II deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 19, 2022
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:: RCV000688278.8

Allele description [Variation Report for NM_000246.4(CIITA):c.566C>T (p.Ala189Val)]

NM_000246.4(CIITA):c.566C>T (p.Ala189Val)

Gene:

CIITA:class II major histocompatibility complex transactivator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.13

Genomic location:

Preferred name:

NM_000246.4(CIITA):c.566C>T (p.Ala189Val)

HGVS:

NC_000016.10:g.10902122C>T
NG_009628.1:g.29925C>T
NM_000246.4:c.566C>TMANE SELECT
NM_001286402.1:c.569C>T
NM_001286403.2:c.482-536C>T
NM_001379330.1:c.485-536C>T
NM_001379331.1:c.482-536C>T
NM_001379332.1:c.569C>T
NM_001379333.1:c.566C>T
NM_001379334.1:c.497C>T
NP_000237.2:p.Ala189Val
NP_000237.2:p.Ala189Val
NP_001273331.1:p.Ala190Val
NP_001366261.1:p.Ala190Val
NP_001366262.1:p.Ala189Val
NP_001366263.1:p.Ala166Val
LRG_49t1:c.566C>T
LRG_49:g.29925C>T
LRG_49p1:p.Ala189Val
NC_000016.9:g.10995979C>T
NM_000246.3:c.566C>T
NR_104444.2:n.695C>T

Protein change:

A166V

Links:

dbSNP: rs149076617

NCBI 1000 Genomes Browser:

rs149076617

Molecular consequence:

NM_001286403.2:c.482-536C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001379330.1:c.485-536C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001379331.1:c.482-536C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000246.4:c.566C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286402.1:c.569C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379332.1:c.569C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379333.1:c.566C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379334.1:c.497C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104444.2:n.695C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: MHC class II deficiency
Synonyms:: BLS, TYPE II; SCID, HLA CLASS II-NEGATIVE; Bare Lymphocyte Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008855; MedGen: C2931418; Orphanet: 572; OMIM: PS209920

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000815883	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 19, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002090698	Natera, Inc.	no assertion criteria provided	Uncertain significance (Oct 28, 2019)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000815883

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 19, 2022)

germline

clinical testing

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

SCV002090698

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Oct 28, 2019)

germline

clinical testing

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, SCV000815883.3

#	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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 189 of the CIITA protein (p.Ala189Val). This variant is present in population databases (rs149076617, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with CIITA-related conditions. ClinVar contains an entry for this variant (Variation ID: 568042). 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 Natera, Inc., SCV002090698.1

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

#	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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