NM_207037.2(TCF12):c.786dup (p.Ser263fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 7, 2023
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:: RCV002538878.2

Allele description [Variation Report for NM_207037.2(TCF12):c.786dup (p.Ser263fs)]

NM_207037.2(TCF12):c.786dup (p.Ser263fs)

Gene:

TCF12:transcription factor 12 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

15q21.3

Genomic location:

Preferred name:

NM_207037.2(TCF12):c.786dup (p.Ser263fs)

HGVS:

NC_000015.10:g.57232391dup
NG_033851.2:g.319302dup
NM_001306219.3:c.276dup
NM_001306220.3:c.118-321dup
NM_001322151.2:c.786dup
NM_001322152.2:c.786dup
NM_001322154.2:c.129dup
NM_001322156.2:c.612dup
NM_001322157.3:c.786dup
NM_001322158.2:c.612dup
NM_001322159.3:c.786dup
NM_001322161.2:c.786dup
NM_001322162.2:c.786dup
NM_001322164.2:c.822dup
NM_001322165.2:c.786dup
NM_003205.4:c.786dup
NM_207036.2:c.786dup
NM_207037.2:c.786dupMANE SELECT
NM_207038.2:c.786dup
NM_207040.2:c.276dup
NP_001293148.1:p.Ser93fs
NP_001309080.1:p.Ser263fs
NP_001309081.1:p.Ser263fs
NP_001309083.1:p.Ser44fs
NP_001309085.1:p.Ser205fs
NP_001309086.1:p.Ser263fs
NP_001309087.1:p.Ser205fs
NP_001309088.1:p.Ser263fs
NP_001309090.1:p.Ser263fs
NP_001309091.1:p.Ser263fs
NP_001309093.1:p.Ser275fs
NP_001309094.1:p.Ser263fs
NP_003196.1:p.Ser263fs
NP_996919.1:p.Ser263fs
NP_996920.1:p.Ser263fs
NP_996921.1:p.Ser263fs
NP_996923.1:p.Ser93fs
NC_000015.9:g.57524587_57524588insA
NC_000015.9:g.57524589dup
NM_207036.1:c.786dupA

Protein change:

S205fs

Links:

dbSNP: rs1597483678

NCBI 1000 Genomes Browser:

rs1597483678

Molecular consequence:

NM_001306219.3:c.276dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322151.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322152.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322154.2:c.129dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322156.2:c.612dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322157.3:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322158.2:c.612dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322159.3:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322161.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322162.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322164.2:c.822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322165.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003205.4:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_207036.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_207037.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_207038.2:c.786dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_207040.2:c.276dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001306220.3:c.118-321dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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TPA_asm: ORF3 [Clonorsi virus 1]
TPA_asm: ORF3 [Clonorsi virus 1]
gi|2234273343|tpg|DAZ87853.1|

Protein
uncharacterized conserved protein [uncultured gamma proteobacterium HF0010_11B23...
uncharacterized conserved protein [uncultured gamma proteobacterium HF0010_11B23]
gi|297180560|gb|ADI16772.1|

Protein
Saccharomyces cerevisiae culture CBS:2910 large subunit ribosomal RNA gene, part...
Saccharomyces cerevisiae culture CBS:2910 large subunit ribosomal RNA gene, partial sequence
gi|1102645680|gb|KY109250.1|

Nucleotide
Saccharomyces cerevisiae strain DBQ22 chromosome 7 centromere and flanking regio...
Saccharomyces cerevisiae strain DBQ22 chromosome 7 centromere and flanking regions genomic sequence
gi|920726587|gb|KT206844.1|

Nucleotide
Saccharomyces cerevisiae 2 micron circle plasmid, complete sequence
Saccharomyces cerevisiae 2 micron circle plasmid, complete sequence
gi|172190|gb|J01347.1|YSCPLASM

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003239322	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23354436, 32620954, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003239322

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 7, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.

Sharma VP, Fenwick AL, Brockop MS, McGowan SJ, Goos JA, Hoogeboom AJ, Brady AF, Jeelani NO, Lynch SA, Mulliken JB, Murray DJ, Phipps JM, Sweeney E, Tomkins SE, Wilson LC, Bennett S, Cornall RJ, Broxholme J, Kanapin A; 500 Whole-Genome Sequences (WGS500) Consortium., Johnson D, Wall SA, et al.

Nat Genet. 2013 Mar;45(3):304-7. doi: 10.1038/ng.2531. Epub 2013 Jan 27. Erratum in: Nat Genet. 2013 Oct;45(10):1261.

PubMed [citation]

PMID:: 23354436
PMCID:: PMC3647333

TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.

Davis EE, Balasubramanian R, Kupchinsky ZA, Keefe DL, Plummer L, Khan K, Meczekalski B, Heath KE, Lopez-Gonzalez V, Ballesta-Martinez MJ, Margabanthu G, Price S, Greening J, Brauner R, Valenzuela I, Cusco I, Fernandez-Alvarez P, Wierman ME, Li T, Lage K, Barroso PS, Chan YM, et al.

Hum Mol Genet. 2020 Aug 11;29(14):2435-2450. doi: 10.1093/hmg/ddaa120.

PubMed [citation]

PMID:: 32620954
PMCID:: PMC7608740

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003239322.2

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 692240). This variant has not been reported in the literature in individuals affected with TCF12-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser263Ilefs*3) in the TCF12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCF12 are known to be pathogenic (PMID: 23354436, 32620954).

#	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: Feb 28, 2024

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