15-40217503-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001211.6(BUB1B):c.2686G>T(p.Asp896Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D896N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001211.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.2686G>T | p.Asp896Tyr | missense_variant | 21/23 | ENST00000287598.11 | |
BUB1B-PAK6 | NM_001128628.3 | c.-365G>T | 5_prime_UTR_variant | 1/11 | |||
LOC107984763 | XR_001751506.2 | n.217+21982C>A | intron_variant, non_coding_transcript_variant | ||||
BUB1B-PAK6 | NM_001128629.3 | c.-282G>T | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.2686G>T | p.Asp896Tyr | missense_variant | 21/23 | 1 | NM_001211.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251464Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461818Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727208
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 29, 2023 | The p.D896Y variant (also known as c.2686G>T), located in coding exon 21 of the BUB1B gene, results from a G to T substitution at nucleotide position 2686. The aspartic acid at codon 896 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at