VCV000021369.25 - ClinVar

NM_003227.4(TFR2):c.1851C>T (p.Ala617=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign
Benign (6)

6 out of 8 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.1851C>T (p.Ala617=)

Variation ID: 21369 Accession: VCV000021369.25

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q22.1 7: 100627408 (GRCh38) [ NCBI UCSC ] 7: 100225031 (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	Feb 15, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_003227.4:c.1851C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003218.2:p.Ala617=	synonymous
NM_001206855.3:c.1338C>T	NP_001193784.1:p.Ala446=	synonymous
NC_000007.14:g.100627408G>A
NC_000007.13:g.100225031G>A
NG_007989.1:g.19143C>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000007.14:100627407:G:A

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.

0.12999 (A)

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

The Genome Aggregation Database (gnomAD) 0.16174

The Genome Aggregation Database (gnomAD) 0.16252

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.16307

The Genome Aggregation Database (gnomAD), exomes 0.17597

The Genome Aggregation Database (gnomAD), exomes 0.19103

Exome Aggregation Consortium (ExAC) 0.24751

1000 Genomes Project 30x 0.12883

1000 Genomes Project 0.12999

Trans-Omics for Precision Medicine (TOPMed) 0.15532

Links

ClinGen: CA341980 dbSNP: rs2075674 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	Benign (3)	criteria provided, multiple submitters, no conflicts	Jul 10, 2021	RCV000020542.10
not specified	Benign (2)	criteria provided, multiple submitters, no conflicts	Mar 4, 2025	RCV000248610.7
Hereditary hemochromatosis	Benign (1)	criteria provided, single submitter	Feb 4, 2026	RCV000355274.12
Hereditary hemochromatosis type 4	Benign (1)	no assertion criteria provided	Sep 16, 2020	RCV001272113.1
not provided	Benign (1)	criteria provided, single submitter	-	RCV004712002.1

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.
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000309476.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Hemochromatosis type 3	Illumina Laboratory Services, Illumina Accession: SCV000465807.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005267707.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Mar 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not specified	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV004025144.2 First in ClinVar: Aug 19, 2023 Last updated: Mar 11, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jul 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hemochromatosis type 3	Genome-Nilou Lab Accession: SCV001762741.2 First in ClinVar: Aug 05, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hereditary hemochromatosis	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001000512.8 First in ClinVar: Dec 17, 2019 Last updated: Feb 15, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Sep 16, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Hereditary hemochromatosis type 4	Natera, Inc. Accession: SCV001453762.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

not provided (-) N Not contributing to aggregate classification	no classification provided	Hemochromatosis type 3	GeneReviews Accession: SCV000041008.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: PubMed (3) PubMed: 11102989‚ 11358389‚ 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

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
TFR2-Related Hemochromatosis.	Adam MP	-	2023	PMID: 20301523
Mutation analysis of the transferrin receptor-2 gene in patients with iron overload.	Lee PL	Blood cells, molecules & diseases	2001	PMID: 11358389
Molecular analysis of the TFR2 gene: report of a novel polymorphism (1878C>T).	Meregalli M	Human mutation	2000	PMID: 11102989

Text-mined citations for rs2075674 ...

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