NM_213653.4(HJV):c.295G>A (p.Gly99Arg) AND not provided

Germline classification:: Likely pathogenic (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:: RCV001378689.7

Allele description [Variation Report for NM_213653.4(HJV):c.295G>A (p.Gly99Arg)]

NM_213653.4(HJV):c.295G>A (p.Gly99Arg)

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.295G>A (p.Gly99Arg)

HGVS:

NC_000001.11:g.146019537C>T
NG_011568.1:g.7286G>A
NM_001316767.2:c.-22+161G>A
NM_001379352.1:c.295G>A
NM_145277.5:c.-45G>A
NM_202004.4:c.-22+161G>A
NM_213652.4:c.-21-837G>A
NM_213653.4:c.295G>AMANE SELECT
NP_001366281.1:p.Gly99Arg
NP_998818.1:p.Gly99Arg
NC_000001.10:g.145415476G>A

Protein change:

G99R

Links:

dbSNP: rs1553769745

NCBI 1000 Genomes Browser:

rs1553769745

Molecular consequence:

NM_145277.5:c.-45G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001316767.2:c.-22+161G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_202004.4:c.-22+161G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_213652.4:c.-21-837G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001379352.1:c.295G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_213653.4:c.295G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001576313	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 19, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 14982873, 19342478, 14647275, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576313

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 19, 2020)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis.

Lanzara C, Roetto A, Daraio F, Rivard S, Ficarella R, Simard H, Cox TM, Cazzola M, Piperno A, Gimenez-Roqueplo AP, Grammatico P, Volinia S, Gasparini P, Camaschella C.

Blood. 2004 Jun 1;103(11):4317-21. Epub 2004 Feb 24.

PubMed [citation]

PMID:: 14982873

Iron overload in the Asian community.

Lok CY, Merryweather-Clarke AT, Viprakasit V, Chinthammitr Y, Srichairatanakool S, Limwongse C, Oleesky D, Robins AJ, Hudson J, Wai P, Premawardhena A, de Silva HJ, Dassanayake A, McKeown C, Jackson M, Gama R, Khan N, Newman W, Banait G, Chilton A, Wilson-Morkeh I, Weatherall DJ, et al.

Blood. 2009 Jul 2;114(1):20-5. doi: 10.1182/blood-2009-01-199109. Epub 2009 Apr 2.

PubMed [citation]

PMID:: 19342478

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576313.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 99 of the HJV protein (p.Gly99Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant has been observed in individual(s) with hereditary hemochromatosis (PMID: 14982873, 19342478). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly99 amino acid residue in HJV. Other variant(s) that disrupt this residue have been observed in individuals with HJV-related conditions (PMID: 14647275), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15").

#	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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