NM_020461.4(TUBGCP6):c.2066-6A>G AND Microcephaly and chorioretinopathy 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jun 7, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000765655.7

Allele description [Variation Report for NM_020461.4(TUBGCP6):c.2066-6A>G]

NM_020461.4(TUBGCP6):c.2066-6A>G

Gene:

TUBGCP6:tubulin gamma complex component 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_020461.4(TUBGCP6):c.2066-6A>G

HGVS:

NC_000022.11:g.50224426T>C
NG_032160.1:g.25546A>G
NM_020461.4:c.2066-6A>GMANE SELECT
NC_000022.10:g.50662855T>C
NM_020461.3:c.2066-6A>G

Links:

dbSNP: rs368765755

NCBI 1000 Genomes Browser:

rs368765755

Molecular consequence:

NM_020461.4:c.2066-6A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Microcephaly and chorioretinopathy 1
Synonyms:: Microcephaly and chorioretinopathy, autosomal recessive, 1
Identifiers:: MONDO: MONDO:0009624; MedGen: C3278481; OMIM: 251270

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000896985	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004101356	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSLVariantClassificationCriteria RUGD 01 April 2020)	Likely pathogenic (Jun 7, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000896985

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 31, 2018)

unknown

clinical testing

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

SCV004101356

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)

Likely pathogenic
(Jun 7, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

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

PMC

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.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000896985.1

#	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

From Illumina Laboratory Services, Illumina, SCV004101356.1

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

Description

The TUBGCP c.2066-6A>G variant occurs in a splice region. This variant has been reported in individuals with clinical features consistent with microcephaly and chorioretinopathy, including in one individual in whom it was confirmed in trans with a likely pathogenic variant in the gene. The c.2066-6A>G variant was shown to segregate with disease in one family in two siblings (PMID: 31077665; 37031378). The highest frequency of this variant in the Genome Aggregation Database is 0.000241 in the African/African American population (version 3.1.2). Functional studies demonstrated that the c.2066-6A>G variant results in the insertion of five intronic nucleotides, which is predicted to lead to a frameshift in the protein reading frame and premature termination of the protein (PMID: 31077665). The c.2066-6A>G variant was identified in trans with a likely pathogenic variant. Based on the available evidence, the c.2066-6A>G variant is classified as likely pathogenic for microcephaly and chorioretinopathy.

#	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: Oct 20, 2024

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