chrX-18174114-TC-T
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_153346.5(BEND2):c.1896del(p.Asn633ThrfsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
BEND2
NM_153346.5 frameshift
NM_153346.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.250
Genes affected
BEND2 (HGNC:28509): (BEN domain containing 2) This gene encodes a protein which has two BEN domains in the C-terminus. These domains are found in proteins which participate in protein and DNA interactions which occur during chromatin restructuring or transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BEND2 | NM_153346.5 | c.1896del | p.Asn633ThrfsTer45 | frameshift_variant | 12/14 | ENST00000380033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BEND2 | ENST00000380033.9 | c.1896del | p.Asn633ThrfsTer45 | frameshift_variant | 12/14 | 1 | NM_153346.5 | P1 | |
BEND2 | ENST00000380030.4 | c.1623del | p.Asn542ThrfsTer45 | frameshift_variant | 10/11 | 1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
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 | GeneDx | Dec 14, 2015 | The c.1896delG variant in the BEND2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1896delG variant causes a frameshift starting with codon Asparagine 633, changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 45 of the new reading frame, denoted p.Asn633ThrfsX45. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1896delG variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1896delG as a variant of uncertain significance. - |
Computational scores
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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