NM_003227.4(TFR2):c.1746del (p.Val583fs) AND Hereditary hemochromatosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 11, 2019
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:: RCV000705183.7

Allele description [Variation Report for NM_003227.4(TFR2):c.1746del (p.Val583fs)]

NM_003227.4(TFR2):c.1746del (p.Val583fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_003227.4(TFR2):c.1746del (p.Val583fs)

HGVS:

NC_000007.13:g.100225221del
NC_000007.14:g.100627599del
NG_007989.1:g.18953del
NM_001206855.3:c.1233del
NM_003227.4:c.1746delMANE SELECT
NP_001193784.1:p.Val412fs
NP_003218.2:p.Val583fs
NC_000007.13:g.100225221del
NC_000007.13:g.100225221delG
NC_000007.13:g.100225222del
NM_003227.3:c.1746delC

Protein change:

V412fs

Links:

dbSNP: rs1562838535

NCBI 1000 Genomes Browser:

rs1562838535

Molecular consequence:

NM_001206855.3:c.1233del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003227.4:c.1746del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000834168	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 11, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23600741, 26029709, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000834168

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 11, 2019)

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

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

Functional consequences of transferrin receptor-2 mutations causing hereditary hemochromatosis type 3.

Joshi R, Shvartsman M, Morán E, Lois S, Aranda J, Barqué A, de la Cruz X, Bruguera M, Vagace JM, Gervasini G, Sanz C, Sánchez M.

Mol Genet Genomic Med. 2015 May;3(3):221-32. doi: 10.1002/mgg3.136. Epub 2015 Mar 6.

PubMed [citation]

PMID:: 26029709
PMCID:: PMC4444164

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000834168.6

#	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. Loss-of-function variants in TFR2 are known to be pathogenic (PMID: 23600741, 26029709). This variant has not been reported in the literature in individuals with TFR2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val583Serfs*87) in the TFR2 gene. It is expected to result in an absent or disrupted protein product.

#	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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