1-146019625-GCCTCCTCCT-GCCTCCTCCTCCTCCT
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3
The NM_213653.4(HJV):c.201_206dupAGGAGG(p.Gly68_Gly69dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,609,004 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G69G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 1 hom. )
Consequence
HJV
NM_213653.4 disruptive_inframe_insertion
NM_213653.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.144
Publications
2 publications found
Genes affected
HJV (HGNC:4887): (hemojuvelin BMP co-receptor) The product of this gene is involved in iron metabolism. It may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression. It could also represent the cellular receptor for hepcidin. Two uORFs in the 5' UTR negatively regulate the expression and activity of the encoded protein. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Defects in this gene are the cause of hemochromatosis type 2A, also called juvenile hemochromatosis (JH). JH is an early-onset autosomal recessive disorder due to severe iron overload resulting in hypogonadotrophic hypogonadism, hepatic fibrosis or cirrhosis and cardiomyopathy, occurring typically before age of 30. [provided by RefSeq, Oct 2015]
HJV Gene-Disease associations (from GenCC):
- hemochromatosis type 2AInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P
- hemochromatosis type 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_213653.4
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_213653.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HJV | MANE Select | c.201_206dupAGGAGG | p.Gly68_Gly69dup | disruptive_inframe_insertion | Exon 3 of 4 | NP_998818.1 | Q6ZVN8-1 | ||
| HJV | c.201_206dupAGGAGG | p.Gly68_Gly69dup | disruptive_inframe_insertion | Exon 3 of 4 | NP_001366281.1 | Q6ZVN8-1 | |||
| HJV | c.-139_-134dupAGGAGG | 5_prime_UTR | Exon 2 of 3 | NP_660320.3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HJV | TSL:2 MANE Select | c.201_206dupAGGAGG | p.Gly68_Gly69dup | disruptive_inframe_insertion | Exon 3 of 4 | ENSP00000337014.5 | Q6ZVN8-1 | ||
| HJV | TSL:1 | c.-139_-134dupAGGAGG | 5_prime_UTR | Exon 2 of 3 | ENSP00000350495.5 | Q6ZVN8-2 | |||
| HJV | TSL:1 | c.-22+67_-22+72dupAGGAGG | intron | N/A | ENSP00000421820.1 | Q6ZVN8-3 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151922Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151922
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad AMR
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000203 AC: 5AN: 246272 AF XY: 0.0000299 show subpopulations
GnomAD2 exomes
AF:
AC:
5
AN:
246272
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1456966Hom.: 1 Cov.: 47 AF XY: 0.0000138 AC XY: 10AN XY: 724932 show subpopulations
GnomAD4 exome
AF:
AC:
16
AN:
1456966
Hom.:
Cov.:
47
AF XY:
AC XY:
10
AN XY:
724932
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33404
American (AMR)
AF:
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26100
East Asian (EAS)
AF:
AC:
0
AN:
39668
South Asian (SAS)
AF:
AC:
15
AN:
86142
European-Finnish (FIN)
AF:
AC:
0
AN:
53094
Middle Eastern (MID)
AF:
AC:
0
AN:
5748
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1107878
Other (OTH)
AF:
AC:
0
AN:
60216
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.439
Heterozygous variant carriers
0
1
2
4
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6
0.00
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000658 AC: 1AN: 152038Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152038
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74336
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41482
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3460
East Asian (EAS)
AF:
AC:
0
AN:
5166
South Asian (SAS)
AF:
AC:
1
AN:
4808
European-Finnish (FIN)
AF:
AC:
0
AN:
10592
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67938
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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