NM_020461.4(TUBGCP6):c.2066-6A>G AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Nov 13, 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:: RCV000766995.34

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]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

PREDICTED: Glycine max putative Myb family transcription factor At1g14600 (LOC10...
PREDICTED: Glycine max putative Myb family transcription factor At1g14600 (LOC102661690), mRNA
gi|2027452535|ref|XM_006575573.3|

Nucleotide
Sample 1
Sample 1

biosample

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000680586	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 22, 2023)	germline	clinical testing	Citation Link,
SCV001249566	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Oct 1, 2019)	germline	clinical testing	Citation Link,
SCV001493483	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31077665, 36307859, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000680586

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 22, 2023)

germline

clinical testing

Citation Link,

SCV001249566

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Oct 1, 2019)

germline

clinical testing

Citation Link,

SCV001493483

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 13, 2023)

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	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and Molecular Characterization of Familial Exudative Vitreoretinopathy Associated With Microcephaly.

Hull S, Arno G, Ostergaard P, Pontikos N, Robson AG, Webster AR, Hogg CR, Wright GA, Henderson RHH, Martin CA, Jackson AP, Mansour S, Moore AT, Michaelides M.

Am J Ophthalmol. 2019 Nov;207:87-98. doi: 10.1016/j.ajo.2019.05.001. Epub 2019 May 8.

PubMed [citation]

PMID:: 31077665

Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses.

Fu F, Li R, Yu Q, Wang D, Deng Q, Li L, Lei T, Chen G, Nie Z, Yang X, Han J, Pan M, Zhen L, Zhang Y, Jing X, Li F, Li F, Zhang L, Yi C, Li Y, Lu Y, Zhou H, et al.

Genome Med. 2022 Oct 28;14(1):123. doi: 10.1186/s13073-022-01130-x.

PubMed [citation]

PMID:: 36307859
PMCID:: PMC9615232

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000680586.5

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

Description

Observed with a second TUBGCP6 variant, phase unknown, in two siblings with familial exudative vitreoretinopathy and microcephaly (Hull et al., 2019); Published functional studies demonstrate a damaging effect secondary to a truncated protein (Hull S et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); Located in a region that tolerates variation and lacks pathogenic variants; This variant is associated with the following publications: (PMID: 33458610, 37031378, 31077665)

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV001249566.26

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001493483.4

#	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 falls in intron 11 of the TUBGCP6 gene. It does not directly change the encoded amino acid sequence of the TUBGCP6 protein. This variant is present in population databases (rs368765755, gnomAD 0.01%). This variant has been observed in individual(s) with clinical features of microcephaly and chorioretinopathy (PMID: 31077665, 36307859). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 437169). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine