NM_000410.4(HFE):c.616+1G>A AND Juvenile hemochromatosis

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 30, 2022
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:: RCV004018185.1

Allele description [Variation Report for NM_000410.4(HFE):c.616+1G>A]

NM_000410.4(HFE):c.616+1G>A

Gene:

HFE:homeostatic iron regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p22.2

Genomic location:

Preferred name:

NM_000410.4(HFE):c.616+1G>A

HGVS:

NC_000006.12:g.26091590G>A
NG_008720.2:g.9310G>A
NM_000410.4:c.616+1G>AMANE SELECT
NM_001300749.3:c.616+1G>A
NM_001384164.1:c.616+1G>A
NM_001406751.1:c.616+1G>A
NM_001406752.1:c.352+1G>A
NM_139003.3:c.340+486G>A
NM_139004.3:c.340+486G>A
NM_139006.3:c.616+1G>A
NM_139007.3:c.352+1G>A
NM_139008.3:c.352+1G>A
NM_139009.3:c.547+1G>A
NM_139010.3:c.77-1095G>A
NM_139011.3:c.77-1529G>A
LRG_748:g.9310G>A
NC_000006.11:g.26091818G>A

Molecular consequence:

NM_139003.3:c.340+486G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_139004.3:c.340+486G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_139010.3:c.77-1095G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_139011.3:c.77-1529G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000410.4:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001300749.3:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001384164.1:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406751.1:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406752.1:c.352+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_139006.3:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_139007.3:c.352+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_139008.3:c.352+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_139009.3:c.547+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Juvenile hemochromatosis
Synonyms:: Hemochromatosis type 2
Identifiers:: MONDO: MONDO:0019257; MedGen: C0268060

Recent activity

Clear Turn Off Turn On

Homo sapiens mediator complex subunit 23 (MED23), transcript variant 11, mRNA
Homo sapiens mediator complex subunit 23 (MED23), transcript variant 11, mRNA
gi|1775987234|ref|NM_001376523.1|

Nucleotide
Mimizuku gurneyi voucher B3294 NADH dehydrogenase subunit 2 (ND2) gene, partial ...
Mimizuku gurneyi voucher B3294 NADH dehydrogenase subunit 2 (ND2) gene, partial cds; mitochondrial
gi|343174751|gb|JN131476.1|

Nucleotide

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
SCV004848700	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Jun 30, 2022)	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

SCV004848700

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Jun 30, 2022)

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

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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848700.1

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

Description

The c.616+1G>A variant in HFE has not been previously reported in individuals with hemochromatosis and was absent from large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the HFE gene is an established disease mechanism in autosomal recessive hemochromatosis. A different variant (c.616+1G>T) has been reported in trans with a pathogenic variant an individual with classical hemochromatosis and segregated in an affected sibling (Wallace 1999 PMID: 10348824). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hemochromatosis type 1. ACMG/AMP criteria applied: PVS1_Strong, PM5, PM2_Supporting.

#	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: May 1, 2024

ClinVar

Relating variation to medicine