NM_001206744.2(TPO):c.1262_1338+54del AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 1, 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:: RCV003567198.1

Allele description [Variation Report for NM_001206744.2(TPO):c.1262_1338+54del]

NM_001206744.2(TPO):c.1262_1338+54del

Gene:

TPO:thyroid peroxidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p25.3

Genomic location:

Preferred name:

NM_001206744.2(TPO):c.1262_1338+54del

HGVS:

NC_000002.12:g.1477528_1477658del
NG_011581.1:g.69066_69196del
NG_011581.2:g.108483_108613del
NM_000547.6:c.1262_1338+54del
NM_001206744.2:c.1262_1338+54delMANE SELECT
NM_001206745.2:c.1262_1338+54del
NM_175719.4:c.1262_1338+54del
NM_175721.3:c.1262_1338+54del
NM_175722.3:c.820-7068_820-6938del
NC_000002.11:g.1481295_1481425del
NC_000002.11:g.1481300_1481430del

Molecular consequence:

NM_175722.3:c.820-7068_820-6938del - intron variant - [Sequence Ontology: SO:0001627]
NM_000547.6:c.1262_1338+54del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001206744.2:c.1262_1338+54del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001206745.2:c.1262_1338+54del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_175719.4:c.1262_1338+54del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_175721.3:c.1262_1338+54del - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV004323248	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 1, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 11061528, 23236987, 25564141, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004323248

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 1, 2023)

germline

clinical testing

PubMed (5)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update).

Bakker B, Bikker H, Vulsma T, de Randamie JS, Wiedijk BM, De Vijlder JJ.

J Clin Endocrinol Metab. 2000 Oct;85(10):3708-12.

PubMed [citation]

PMID:: 11061528

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004323248.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals affected with TPO-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant results in the deletion of part of exon 8 (c.1262_1338+54del) of the TPO gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TPO are known to be pathogenic (PMID: 11061528, 23236987, 25564141).

#	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 20, 2024

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