VCV000005380.3 - ClinVar

NM_003227.4(TFR2):c.750C>G (p.Tyr250Ter)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

1 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_003227.4(TFR2):c.750C>G (p.Tyr250Ter)

Variation ID: 5380 Accession: VCV000005380.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q22.1 7: 100633100 (GRCh38) [ NCBI UCSC ] 7: 100230723 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Oct 1, 2022	May 1, 2000

HGVS

Nucleotide	Protein	Molecular consequence
NM_003227.4:c.750C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003218.2:p.Tyr250Ter	nonsense
NM_001206855.3:c.237C>G	NP_001193784.1:p.Tyr79Ter	nonsense
NC_000007.14:g.100633100G>C
NC_000007.13:g.100230723G>C
NG_007989.1:g.13451C>G

... more HGVS ... less HGVS

Protein change

Y250*, Y79*

Other names

Canonical SPDI

NC_000007.14:100633099:G:C

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00000

Links

OMIM: 604720.0001 dbSNP: rs80338880 ClinGen: CA340407 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TFR2		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1079	1215

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hemochromatosis type 3	Pathogenic (2)	no assertion criteria provided	May 1, 2000	RCV000005711.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 01, 2000) C Contributing to aggregate classification	no assertion criteria provided	HEMOCHROMATOSIS, TYPE 3	OMIM Accession: SCV000025893.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 28, 2018	Publications: PubMed (1) PubMed: 10802645 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In 2 families from Sicily who met diagnostic criteria for hemochromatosis (HFE3; 604250) but were not linked to the HFE locus (235200), one of which … (more) In 2 families from Sicily who met diagnostic criteria for hemochromatosis (HFE3; 604250) but were not linked to the HFE locus (235200), one of which was consanguineous, Camaschella et al. (2000) identified a C-to-G transversion in exon 6 at position 750 of the TFR2 cDNA sequence, resulting in a tyrosine (TAC)-to-stop (TAG) substitution at residue 250 (Y250X). This substitution created a MaeI site. All affected members of the consanguineous family were homozygous for Y250X, whereas obligate carriers were heterozygous. One patient in the nonconsanguineous family was homozygous for this mutation. Camaschella et al. (2000) did not find the Y250X mutation in 100 normal chromosomes or in 12 hemochromatosis patients who did not have mutations in HFE. (less)

not provided (-) N Not contributing to aggregate classification	no classification provided	Hemochromatosis type 3	GeneReviews Accession: SCV000041020.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: PubMed (2) PubMed: 10802645‚ 20301523 BookShelf: NBK1349 BookShelf: NBK1349 Observation: 1 Collection method: literature only Allele origin: unknown Affected status: not provided Observation 1 Collection method: literature only Allele origin: unknown Affected status: not provided

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
TFR2-Related Hemochromatosis.	Adam MP	-	2023	PMID: 20301523
The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22.	Camaschella C	Nature genetics	2000	PMID: 10802645

Text-mined citations for rs80338880 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 06, 2026