chr21-37505276-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001347721.2(DYRK1A):​c.1213-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DYRK1A
NM_001347721.2 splice_region, intron

Scores

2
Splicing: ADA: 0.00006881
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00
Variant links:
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYRK1ANM_001347721.2 linkc.1213-7C>A splice_region_variant, intron_variant Intron 9 of 11 ENST00000647188.2 NP_001334650.1 Q13627-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYRK1AENST00000647188.2 linkc.1213-7C>A splice_region_variant, intron_variant Intron 9 of 11 NM_001347721.2 ENSP00000494572.1 Q13627-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1449724
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
719712
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32958
American (AMR)
AF:
0.00
AC:
0
AN:
43562
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25594
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39470
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85360
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53224
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5692
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1104036
Other (OTH)
AF:
0.00
AC:
0
AN:
59828
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
2.5
DANN
Benign
0.41
PhyloP100
0.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000069
dbscSNV1_RF
Benign
0.034
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs199867876; hg19: chr21-38877579; API