NM_001365276.2(TNXB):c.12469+2T>C AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Apr 10, 2024
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:: RCV000519700.7

Allele description [Variation Report for NM_001365276.2(TNXB):c.12469+2T>C]

NM_001365276.2(TNXB):c.12469+2T>C

Genes:

LOC106780803:tenascin XB recombination region [Gene]
TNXB:tenascin XB [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.33

Genomic location:

Preferred name:

NM_001365276.2(TNXB):c.12469+2T>C

HGVS:

NC_000006.12:g.32042010A>G
NG_007941.3:g.8706A>G
NG_008337.2:g.72365T>C
NG_045227.1:g.503A>G
NM_001365276.2:c.12469+2T>CMANE SELECT
NM_019105.8:c.12463+2T>C
NM_032470.4:c.1756+2T>C
LRG_829:g.8706A>G
NC_000006.11:g.32009787A>G
NM_019105.6:c.12463+2T>C
NM_019105.8:c.12463+2T>C
NM_032470.3:c.1756+2T>C

Links:

dbSNP: rs545719209

NCBI 1000 Genomes Browser:

rs545719209

Molecular consequence:

NM_001365276.2:c.12469+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_019105.8:c.12463+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_032470.4:c.1756+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000618266	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 10, 2024)	germline	clinical testing	Citation Link,
SCV004227207	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 6, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33332743, 25741868
SCV005188854	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000618266

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Apr 10, 2024)

germline

clinical testing

Citation Link,

SCV004227207

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 6, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005188854

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

germline

not provided

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, not provided
not provided	germline	unknown	7	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A TNXB splice donor site variant as a cause of hypermobility type Ehlers-Danlos syndrome in patients with congenital adrenal hyperplasia.

Lao Q, Mallappa A, Rueda Faucz F, Joyal E, Veeraraghavan P, Chen W, Merke DP.

Mol Genet Genomic Med. 2021 Feb;9(2):e1556. doi: 10.1002/mgg3.1556. Epub 2020 Dec 17.

PubMed [citation]

PMID:: 33332743
PMCID:: PMC8077117

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

Details of each submission

From GeneDx, SCV000618266.5

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

Description

Observed in the heterozygous state in individuals with clinical features of EhlersDanlos syndrome and a diagnosis of congenital adrenal hyperplasia (PMID: 33332743); Published functional studies suggest that the c.12463+2T>C variant reduces the splicing efficiency at TNXB intron 42 via an allele-specific decrease in mRNA (PMID: 33332743); In silico analysis indicates that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 33332743)

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004227207.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	PubMed (2)

Description

BS1, BP4, BP7, PS3_supporting, PVS1_strong

#	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		7	not provided	not provided	not provided

From Breakthrough Genomics, Breakthrough Genomics, SCV005188854.1

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

#	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

Last Updated: Nov 18, 2024

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