NM_213653.4(HJV):c.976C>T (p.Arg326Ter) AND Hemochromatosis type 2A

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jul 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000002463.16

Allele description [Variation Report for NM_213653.4(HJV):c.976C>T (p.Arg326Ter)]

NM_213653.4(HJV):c.976C>T (p.Arg326Ter)

Gene:

HJV:hemojuvelin BMP co-receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.1

Genomic location:

Preferred name:

NM_213653.4(HJV):c.976C>T (p.Arg326Ter)

HGVS:

NC_000001.11:g.146018382G>A
NG_011568.1:g.8441C>T
NM_001316767.2:c.298C>T
NM_001379352.1:c.976C>T
NM_145277.5:c.637C>T
NM_202004.4:c.298C>T
NM_213652.4:c.298C>T
NM_213653.4:c.976C>TMANE SELECT
NP_001303696.1:p.Arg100Ter
NP_001366281.1:p.Arg326Ter
NP_660320.3:p.Arg213Ter
NP_973733.1:p.Arg100Ter
NP_998817.1:p.Arg100Ter
NP_998818.1:p.Arg326Ter
NP_998818.1:p.Arg326Ter
NC_000001.10:g.145416631C>T
NM_213653.3:c.976C>T

Protein change:

R100*; ARG326TER

Links:

OMIM: 608374.0002; dbSNP: rs74315324

NCBI 1000 Genomes Browser:

rs74315324

Molecular consequence:

NM_001316767.2:c.298C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001379352.1:c.976C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_145277.5:c.637C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_202004.4:c.298C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_213652.4:c.298C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_213653.4:c.976C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hemochromatosis type 2A (HFE2A)
Identifiers:: MONDO: MONDO:0011216; MedGen: C1865614; Orphanet: 79230; OMIM: 602390

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022621	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2004)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000915352	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSLVariantClassificationCriteria RUGD 01 April 2020)	Pathogenic (Jul 22, 2024)	unknown	clinical testing	Citation Link,
SCV002085768	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Aug 25, 2021)	germline	clinical testing
SCV003845121	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jan 12, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15710580, 26151776, 14647275, 15194541, 32824233 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Hemojuvelin (HJV)-associated hemochromatosis: analysis of HJV and HFE mutations and iron overload in three families.

Wallace DF, Dixon JL, Ramm GA, Anderson GJ, Powell LW, Subramaniam N.

Haematologica. 2005 Feb;90(2):254-5.

PubMed [citation]

PMID:: 15710580

Next-generation sequencing: Application of a novel platform to analyze atypical iron disorders.

McDonald CJ, Ostini L, Wallace DF, Lyons A, Crawford DH, Subramaniam VN.

J Hepatol. 2015 Nov;63(5):1288-93. doi: 10.1016/j.jhep.2015.06.027. Epub 2015 Jul 4. Review.

PubMed [citation]

PMID:: 26151776

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000022621.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the arg326-to-ter (R326X) mutation in the HJV gene that was found in compound heterozygous state in patients with juvenile hemochromatosis (HFE2A; 602390) by Papanikolaou et al. (2004), see 608374.0001.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV000915352.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002085768.1

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

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003845121.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: HJV c.976C>T (p.Arg326X) results in a premature termination codon located in the last exon, therefore not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein, removing a large part of the 426 amino acid long protein (InterPro). Truncations downstream of this position have been reported in affected individuals (HGMD). The variant allele was found at a frequency of 1.2e-05 in 251340 control chromosomes (gnomAD). c.976C>T has been reported in the literature in compound heterozygous individuals affected with Hemochromatosis Type 2A (Papanikolaou_2003, Wallace_2004). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was 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

ClinVar

Relating variation to medicine