rs7482144
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The ENST00000380252.6(HBG2):c.-73-425C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 560,744 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.21 ( 15 hom., cov: 29)
Exomes 𝑓: 0.22 ( 1 hom. )
Consequence
HBG2
ENST00000380252.6 intron
ENST00000380252.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.541
Genes affected
HBG2 (HGNC:4832): (hemoglobin subunit gamma 2) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'- epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 11-5254939-G-A is Benign according to our data. Variant chr11-5254939-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 14984.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBG2 | ENST00000380252.6 | c.-73-425C>T | intron_variant | 3 | |||||
ENST00000646569.1 | n.506C>T | non_coding_transcript_exon_variant | 5/5 |
Frequencies
GnomAD3 genomes ? AF: 0.207 AC: 31089AN: 150068Hom.: 15 Cov.: 29
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GnomAD4 exome AF: 0.218 AC: 89641AN: 410562Hom.: 1 Cov.: 0 AF XY: 0.219 AC XY: 47503AN XY: 216468
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GnomAD4 genome ? AF: 0.207 AC: 31096AN: 150182Hom.: 15 Cov.: 29 AF XY: 0.203 AC XY: 14930AN XY: 73372
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Hereditary persistence of fetal hemoglobin Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Dec 01, 2010 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 09, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at