21-43613852-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007031.2(HSF2BP):c.670G>T(p.Gly224*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000508 in 1,612,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
HSF2BP
NM_007031.2 stop_gained
NM_007031.2 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.33
Genes affected
HSF2BP (HGNC:5226): (heat shock transcription factor 2 binding protein) HSF2 binding protein (HSF2BP) associates with HSF2. The interaction occurs between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper motifs. HSF2BP may therefore be involved in modulating HSF2 activation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSF2BP | NM_007031.2 | c.670G>T | p.Gly224* | stop_gained | 7/9 | ENST00000291560.7 | NP_008962.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSF2BP | ENST00000291560.7 | c.670G>T | p.Gly224* | stop_gained | 7/9 | 1 | NM_007031.2 | ENSP00000291560.2 | ||
HSF2BP | ENST00000443485.1 | c.679G>T | p.???227??? | splice_region_variant, synonymous_variant | 7/7 | 5 | ENSP00000409585.1 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152132Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251240Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135774
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1460828Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32AN XY: 726782
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74316
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2024 | HSF2BP: PM2 - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
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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