NM_003227.4(TFR2):c.2095_2096del (p.Asp699fs) AND Hereditary hemochromatosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 23, 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:: RCV001388574.5

Allele description [Variation Report for NM_003227.4(TFR2):c.2095_2096del (p.Asp699fs)]

NM_003227.4(TFR2):c.2095_2096del (p.Asp699fs)

Genes:

LOC113687175:Sharpr-MPRA regulatory region 4647 [Gene]
TFR2:transferrin receptor 2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_003227.4(TFR2):c.2095_2096del (p.Asp699fs)

HGVS:

NC_000007.14:g.100626803TC[3]
NG_007989.1:g.19741GA[3]
NG_062456.1:g.298TC[3]
NM_001206855.3:c.1582_1583del
NM_003227.4:c.2095_2096delMANE SELECT
NP_001193784.1:p.Asp528fs
NP_003218.2:p.Asp699fs
NC_000007.13:g.100224426TC[3]
NC_000007.13:g.100224426_100224427del

Protein change:

D528fs

Links:

dbSNP: rs1562837561

NCBI 1000 Genomes Browser:

rs1562837561

Molecular consequence:

NM_001206855.3:c.1582_1583del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003227.4:c.2095_2096del - 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
SCV001589621	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 23, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001589621

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 23, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001589621.4

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

Description

This variant has not been reported in the literature in individuals affected with TFR2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Asp699Argfs*92) in the TFR2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 103 amino acid(s) of the TFR2 protein. This variant disrupts a region of the TFR2 protein in which other variant(s) (p.Ile710Alafs*80) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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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