NM_000410.4(HFE):c.502G>T (p.Glu168Ter) AND Hereditary hemochromatosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 29, 2022
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:: RCV001058987.14

Allele description [Variation Report for NM_000410.4(HFE):c.502G>T (p.Glu168Ter)]

NM_000410.4(HFE):c.502G>T (p.Glu168Ter)

Gene:

HFE:homeostatic iron regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p22.2

Genomic location:

Preferred name:

NM_000410.4(HFE):c.502G>T (p.Glu168Ter)

HGVS:

NC_000006.12:g.26091475G>T
NG_008720.2:g.9195G>T
NM_000410.4:c.502G>TMANE SELECT
NM_001300749.3:c.502G>T
NM_001384164.1:c.502G>T
NM_001406751.1:c.502G>T
NM_001406752.1:c.238G>T
NM_139003.3:c.340+371G>T
NM_139004.3:c.340+371G>T
NM_139006.3:c.502G>T
NM_139007.3:c.238G>T
NM_139008.3:c.238G>T
NM_139009.3:c.433G>T
NM_139010.3:c.77-1210G>T
NM_139011.3:c.77-1644G>T
NP_000401.1:p.Glu168Ter
NP_000401.1:p.Glu168Ter
NP_001287678.1:p.Glu168Ter
NP_001287678.1:p.Glu168Ter
NP_001371093.1:p.Glu168Ter
NP_001393680.1:p.Glu168Ter
NP_001393681.1:p.Glu80Ter
NP_620575.1:p.Glu168Ter
NP_620576.1:p.Glu80Ter
NP_620577.1:p.Glu80Ter
NP_620578.1:p.Glu145Ter
LRG_748t1:c.502G>T
LRG_748:g.9195G>T
LRG_748p1:p.Glu168Ter
NC_000006.11:g.26091703G>T
NM_000410.3:c.502G>T
NM_001300749.2:c.502G>T

Protein change:

E145*

Links:

dbSNP: rs146519482

NCBI 1000 Genomes Browser:

rs146519482

Molecular consequence:

NM_139003.3:c.340+371G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_139004.3:c.340+371G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_139010.3:c.77-1210G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_139011.3:c.77-1644G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000410.4:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001300749.3:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001384164.1:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406751.1:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406752.1:c.238G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139006.3:c.502G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139007.3:c.238G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139008.3:c.238G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139009.3:c.433G>T - 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
SCV001223590	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10930379, 27518069, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001223590

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 29, 2022)

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

Two novel nonsense mutations of HFE gene in five unrelated italian patients with hemochromatosis.

Piperno A, Arosio C, Fossati L, Viganò M, Trombini P, Vergani A, Mancia G.

Gastroenterology. 2000 Aug;119(2):441-5.

PubMed [citation]

PMID:: 10930379

Rare HFE variants are the most frequent cause of hemochromatosis in non-c282y homozygous patients with hemochromatosis.

Hamdi-Rozé H, Beaumont-Epinette MP, Ben Ali Z, Le Lan C, Loustaud-Ratti V, Causse X, Loreal O, Deugnier Y, Brissot P, Jouanolle AM, Bardou-Jacquet E.

Am J Hematol. 2016 Dec;91(12):1202-1205. doi: 10.1002/ajh.24535. Epub 2016 Aug 22.

PubMed [citation]

PMID:: 27518069

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001223590.5

#	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: 88946). This premature translational stop signal has been observed in individuals with hemochromatosis (PMID: 10930379). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu168*) in the HFE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HFE are known to be pathogenic (PMID: 27518069).

#	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: Nov 3, 2024

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