NM_000397.4(CYBB):c.607G>T (p.Glu203Ter) AND Granulomatous disease, chronic, X-linked

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 14, 2018
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:: RCV000029630.10

Allele description [Variation Report for NM_000397.4(CYBB):c.607G>T (p.Glu203Ter)]

NM_000397.4(CYBB):c.607G>T (p.Glu203Ter)

Gene:

CYBB:cytochrome b-245 beta chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_000397.4(CYBB):c.607G>T (p.Glu203Ter)

HGVS:

NC_000023.11:g.37796074G>T
NG_009065.1:g.21054G>T
NM_000397.4:c.607G>TMANE SELECT
NP_000388.2:p.Glu203Ter
NP_000388.2:p.Glu203Ter
LRG_53t1:c.607G>T
LRG_53:g.21054G>T
LRG_53p1:p.Glu203Ter
NC_000023.10:g.37655327G>T
NM_000397.3:c.607G>T
p.Glu203X

Protein change:

E203*

Links:

dbSNP: rs193922449

NCBI 1000 Genomes Browser:

rs193922449

Molecular consequence:

NM_000397.4:c.607G>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Granulomatous disease, chronic, X-linked
Synonyms:: CYTOCHROME b-NEGATIVE GRANULOMATOUS DISEASE, CHRONIC, X-LINKED; GRANULOMATOUS DISEASE, CHRONIC, X-LINKED, SOMATIC MOSAIC
Identifiers:: MONDO: MONDO:0010600; MedGen: C1844376; Orphanet: 379; OMIM: 306400

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RecName: Full=E3 ubiquitin-protein ligase Topors; AltName: Full=RING-type E3 ubi...
RecName: Full=E3 ubiquitin-protein ligase Topors; AltName: Full=RING-type E3 ubiquitin transferase Topors; AltName: Full=SUMO1-protein E3 ligase Topors; AltName: Full=Topoisomerase I-binding RING finger protein; AltName: Full=Topoisomerase I-binding arginine/serine-rich protein; AltName: Full=Tumor suppressor p53-binding protein 3; Short=p53-binding protein 3; Short=p53BP3
gi|74752935|sp|Q9NS56.1|TOPRS_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000052282	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	likely pathogenic (Aug 18, 2011)	germline	curation, clinical testing	PubMed (3) [See all records that cite these PMIDs] 11162142, 8961628, 8634410 Citation Link,
SCV000943366	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 14, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9585602, 20729109, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000052282

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

likely pathogenic
(Aug 18, 2011)

germline

curation, clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000943366

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 14, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	curation
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hematologically important mutations: X-linked chronic granulomatous disease (second update).

Heyworth PG, Curnutte JT, Rae J, Noack D, Roos D, van Koppen E, Cross AR.

Blood Cells Mol Dis. 2001 Jan-Feb;27(1):16-26. No abstract available.

PubMed [citation]

PMID:: 11162142

X-CGDbase: a database of X-CGD-causing mutations.

Roos D.

Immunol Today. 1996 Nov;17(11):517-21. No abstract available.

PubMed [citation]

PMID:: 8961628

See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052282.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	curation	PubMed (3)
2	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

"X-CGD; controls not tested.": PubMed [ID: 8634410]

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	See 2

Co-occurrences

#	Zygosity	Alleles	Number of Observations
2	Homozygote	CYBB:c.1002G>A	1

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000943366.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Glu203*) in the CYBB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with chronic granulomatous disease¬†(PMID:¬†8634410,¬†20729109). ClinVar contains an entry for this variant (Variation ID: 35974). Loss-of-function variants in CYBB are known to be pathogenic (PMID: 9585602, 20729109). For these reasons, this variant has been classified as Pathogenic.

#	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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