NM_016495.6(TBC1D7):c.322dup (p.Tyr108fs) AND Macrocephaly/megalencephaly syndrome, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 16, 2024
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:: RCV003994474.1

Allele description [Variation Report for NM_016495.6(TBC1D7):c.322dup (p.Tyr108fs)]

NM_016495.6(TBC1D7):c.322dup (p.Tyr108fs)

Genes:

TBC1D7:TBC1 domain family member 7 [Gene - OMIM - HGNC]
TBC1D7-LOC100130357:TBC1D7-LOC100130357 readthrough [Gene]

Variant type:

Duplication

Cytogenetic location:

6p24.1

Genomic location:

Preferred name:

NM_016495.6(TBC1D7):c.322dup (p.Tyr108fs)

HGVS:

NC_000006.12:g.13320967dup
NG_033862.1:g.12617dup
NM_001143964.4:c.322dup
NM_001143965.4:c.322dup
NM_001143966.4:c.241dup
NM_001258457.3:c.322dup
NM_001318805.2:c.322dup
NM_001318806.2:c.241dup
NM_001318809.2:c.322dup
NM_016495.6:c.322dupMANE SELECT
NP_001137436.1:p.Tyr108fs
NP_001137437.1:p.Tyr108fs
NP_001137438.1:p.Tyr81fs
NP_001245386.1:p.Tyr108fs
NP_001305734.1:p.Tyr108fs
NP_001305735.1:p.Tyr81fs
NP_001305738.1:p.Tyr108fs
NP_057579.1:p.Tyr108fs
NC_000006.11:g.13321198_13321199insA
NC_000006.11:g.13321199dup
NM_001143965.4:c.322dupT
NR_134872.2:n.412dup

Protein change:

Y108fs

Molecular consequence:

NM_001143964.4:c.322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001143965.4:c.322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001143966.4:c.241dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258457.3:c.322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318805.2:c.322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318806.2:c.241dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318809.2:c.322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_016495.6:c.322dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_134872.2:n.412dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Macrocephaly/megalencephaly syndrome, autosomal recessive (MGCPH)
Synonyms:: Fryns Dereymaeker Haegeman syndrome
Identifiers:: MONDO: MONDO:0009544; MedGen: C3806412; OMIM: 248000

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PREDICTED: Corvus hawaiiensis dpy-19 like C-mannosyltransferase 3 (DPY19L3), transcript variant X3, mRNA
gi|2240466745|ref|XM_048317135.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004813799	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 16, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004813799

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Feb 16, 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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004813799.1

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

Description

Variant summary: TBC1D7 c.322dupT (p.Tyr108LeufsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 251480 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.322dupT in individuals affected with Macrocephaly/megalencephaly Syndrome, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2062902). Based on the evidence outlined above, the variant was 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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