NM_006060.6(IKZF1):c.56C>A (p.Pro19His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 2, 2024
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:: RCV002857230.4

Allele description [Variation Report for NM_006060.6(IKZF1):c.56C>A (p.Pro19His)]

NM_006060.6(IKZF1):c.56C>A (p.Pro19His)

Gene:

IKZF1:IKAROS family zinc finger 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p12.2

Genomic location:

Preferred name:

NM_006060.6(IKZF1):c.56C>A (p.Pro19His)

HGVS:

NC_000007.14:g.50327653C>A
NG_034231.1:g.28571C>A
NM_001220765.3:c.56C>A
NM_001220767.2:c.56C>A
NM_001220768.2:c.56C>A
NM_001220770.2:c.56C>A
NM_001220771.2:c.56C>A
NM_001291837.2:c.56C>A
NM_001291838.2:c.56C>A
NM_001291839.2:c.56C>A
NM_001291840.1:c.56C>A
NM_001291841.1:c.56C>A
NM_001291842.1:c.56C>A
NM_001291843.1:c.56C>A
NM_001291844.1:c.56C>A
NM_001291845.2:c.56C>A
NM_001291846.2:c.56C>A
NM_001291847.2:c.56C>A
NM_001410879.1:c.56C>A
NM_006060.5:c.56C>A
NM_006060.6:c.56C>AMANE SELECT
NP_001207694.1:p.Pro19His
NP_001207696.1:p.Pro19His
NP_001207697.1:p.Pro19His
NP_001207699.1:p.Pro19His
NP_001207700.1:p.Pro19His
NP_001278766.1:p.Pro19His
NP_001278767.1:p.Pro19His
NP_001278768.1:p.Pro19His
NP_001278769.1:p.Pro19His
NP_001278770.1:p.Pro19His
NP_001278771.1:p.Pro19His
NP_001278772.1:p.Pro19His
NP_001278773.1:p.Pro19His
NP_001278774.1:p.Pro19His
NP_001278775.1:p.Pro19His
NP_001278776.1:p.Pro19His
NP_001397808.1:p.Pro19His
NP_006051.1:p.Pro19His
LRG_1121t1:c.56C>A
LRG_1121:g.28571C>A
LRG_1121p1:p.Pro19His
NC_000007.13:g.50367249C>A

Protein change:

P19H

Molecular consequence:

NM_001220765.3:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001220767.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001220768.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001220770.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001220771.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291837.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291838.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291839.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291840.1:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291841.1:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291842.1:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291843.1:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291844.1:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291845.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291846.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291847.2:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001410879.1:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006060.6:c.56C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003224058	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 29, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005389914	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 2, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003224058

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 29, 2022)

germline

clinical testing

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

SCV005389914

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Apr 2, 2024)

germline

clinical testing

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
not provided	germline	yes	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, SCV003224058.2

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

Description

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 sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 19 of the IKZF1 protein (p.Pro19His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IKZF1-related conditions. 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available").

#	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 GeneDx, SCV005389914.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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