NM_003227.4(TFR2):c.750del (p.His249_Tyr250insTer) AND Hereditary hemochromatosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 16, 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:: RCV003752112.2

Allele description [Variation Report for NM_003227.4(TFR2):c.750del (p.His249_Tyr250insTer)]

NM_003227.4(TFR2):c.750del (p.His249_Tyr250insTer)

Gene:

TFR2:transferrin receptor 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_003227.4(TFR2):c.750del (p.His249_Tyr250insTer)

HGVS:

NC_000007.14:g.100633100del
NG_007989.1:g.13451del
NM_001206855.3:c.237del
NM_003227.4:c.750delMANE SELECT
NP_001193784.1:p.His78_Tyr79insTer
NP_003218.2:p.His249_Tyr250insTer
NC_000007.13:g.100230723del

Molecular consequence:

NM_001206855.3:c.237del - nonsense - [Sequence Ontology: SO:0001587]
NM_003227.4:c.750del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary hemochromatosis (HFE)
Identifiers:: MONDO: MONDO:0006507; MedGen: C0392514; OMIM: PS235200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004437883	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 16, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12134060, 23600741, 26029709, 10802645, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004437883

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 16, 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

Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis.

Fleming RE, Ahmann JR, Migas MC, Waheed A, Koeffler HP, Kawabata H, Britton RS, Bacon BR, Sly WS.

Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10653-8. Epub 2002 Jul 19.

PubMed [citation]

PMID:: 12134060
PMCID:: PMC125003

Variable age of onset and clinical severity in transferrin receptor 2 related haemochromatosis: novel observations.

Bardou-Jacquet E, Cunat S, Beaumont-Epinette MP, Kannengiesser C, Causse X, Sauvion S, Pouliquen B, Deugnier Y, David V, Loréal O, Aguilar-Martinez P, Brissot P, Jouanolle AM.

Br J Haematol. 2013 Jul;162(2):278-81. doi: 10.1111/bjh.12350. Epub 2013 Apr 18. No abstract available.

PubMed [citation]

PMID:: 23600741

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004437883.1

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

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this premature translational stop signal affects TFR2 function (PMID: 12134060). This sequence change creates a premature translational stop signal (p.Tyr250*) in the TFR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TFR2 are known to be pathogenic (PMID: 23600741, 26029709). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with haemochromatosis (PMID: 10802645). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant.

#	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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