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NM_213653.4(HJV):c.950G>A (p.Cys317Tyr) AND Hemochromatosis type 2A

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 19, 2020
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:
RCV002470996.1

Allele description [Variation Report for NM_213653.4(HJV):c.950G>A (p.Cys317Tyr)]

NM_213653.4(HJV):c.950G>A (p.Cys317Tyr)

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.950G>A (p.Cys317Tyr)
HGVS:
  • NC_000001.11:g.146018408C>T
  • NG_011568.1:g.8415G>A
  • NM_001316767.2:c.272G>A
  • NM_001379352.1:c.950G>A
  • NM_145277.5:c.611G>A
  • NM_202004.4:c.272G>A
  • NM_213652.4:c.272G>A
  • NM_213653.4:c.950G>AMANE SELECT
  • NP_001303696.1:p.Cys91Tyr
  • NP_001366281.1:p.Cys317Tyr
  • NP_660320.3:p.Cys204Tyr
  • NP_973733.1:p.Cys91Tyr
  • NP_998817.1:p.Cys91Tyr
  • NP_998818.1:p.Cys317Tyr
  • NP_998818.1:p.Cys317Tyr
  • NC_000001.10:g.145416605G>A
  • NM_213653.3:c.950G>A
Protein change:
C204Y
Links:
dbSNP: rs1553769457
NCBI 1000 Genomes Browser:
rs1553769457
Molecular consequence:
  • NM_001316767.2:c.272G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379352.1:c.950G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_145277.5:c.611G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_202004.4:c.272G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_213652.4:c.272G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_213653.4:c.950G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002767147Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 19, 2020) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A severe hemojuvelin mutation leading to late onset of HFE2-hemochromatosis.

Ravasi G, Pelucchi S, Mariani R, Silvestri L, Camaschella C, Piperno A.

Dig Liver Dis. 2018 Aug;50(8):859-862. doi: 10.1016/j.dld.2018.04.018. Epub 2018 Apr 27. No abstract available.

PubMed [citation]
PMID:
29764732

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767147.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as 3A-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with haemachromatosis type 2A (MIM#602390). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from cysteine to tyrosine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change p.(Cys317Ser) at the same position has been observed in gnomAD (v2) (2 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated RGM C-terminal domain (Pfam). (I) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. One individual with late-onset haemachromatosis was reported with the homozygous comparable variant p.(Cys317Ser). Functional studies of this variant were supportive of impaired function (PMID: 29764732). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. There is one likely pathogenic assertion for this variant in the ClinVar database. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024