rs1057523364
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_StrongBP6_Very_StrongBP7BS1BS2_Supporting
The NM_001347721.2(DYRK1A):āc.795T>Cā(p.Leu265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 30)
Exomes š: 0.0000096 ( 0 hom. )
Consequence
DYRK1A
NM_001347721.2 synonymous
NM_001347721.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.434
Genes affected
DYRK1A (HGNC:3091): (dual specificity tyrosine phosphorylation regulated kinase 1A) This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a nuclear targeting signal sequence, a protein kinase domain, a leucine zipper motif, and a highly conservative 13-consecutive-histidine repeat. It catalyzes its autophosphorylation on serine/threonine and tyrosine residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of Drosophila mnb (minibrain) gene and rat Dyrk gene. It is localized in the Down syndrome critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 21-37490332-T-C is Benign according to our data. Variant chr21-37490332-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 389219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.434 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000132 (2/152024) while in subpopulation SAS AF= 0.000414 (2/4830). AF 95% confidence interval is 0.0000729. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 14 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYRK1A | NM_001347721.2 | c.795T>C | p.Leu265= | synonymous_variant | 7/12 | ENST00000647188.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYRK1A | ENST00000647188.2 | c.795T>C | p.Leu265= | synonymous_variant | 7/12 | NM_001347721.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152024Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251366Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461608Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727104
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152024Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2AN XY: 74278
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 12, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 12, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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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