19-55308657-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_032430.2(BRSK1):c.2108A>G(p.Lys703Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000785 in 1,604,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 24)
Exomes 𝑓: 0.000085 ( 0 hom. )
Consequence
BRSK1
NM_032430.2 missense
NM_032430.2 missense
Scores
1
2
11
Clinical Significance
Conservation
PhyloP100: 5.03
Genes affected
BRSK1 (HGNC:18994): (BR serine/threonine kinase 1) Enables magnesium ion binding activity; protein serine/threonine kinase activity; and tau-protein kinase activity. Involved in mitotic G2 DNA damage checkpoint signaling and protein phosphorylation. Acts upstream of or within G2/M transition of mitotic cell cycle; peptidyl-serine phosphorylation; and response to UV. Located in cell junction; cytoplasm; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, BRSK1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18626171).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRSK1 | NM_032430.2 | c.2108A>G | p.Lys703Arg | missense_variant | 18/19 | ENST00000309383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRSK1 | ENST00000309383.6 | c.2108A>G | p.Lys703Arg | missense_variant | 18/19 | 1 | NM_032430.2 | P1 | |
BRSK1 | ENST00000590333.5 | c.2156A>G | p.Lys719Arg | missense_variant | 20/21 | 1 | |||
BRSK1 | ENST00000326848.7 | c.1193A>G | p.Lys398Arg | missense_variant | 10/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000134 AC: 2AN: 149726Hom.: 0 Cov.: 24
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250158Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135404
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GnomAD4 exome AF: 0.0000852 AC: 124AN: 1454784Hom.: 0 Cov.: 32 AF XY: 0.0000829 AC XY: 60AN XY: 723804
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GnomAD4 genome ? AF: 0.0000134 AC: 2AN: 149726Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 73002
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The c.2108A>G (p.K703R) alteration is located in exon 18 (coding exon 18) of the BRSK1 gene. This alteration results from a A to G substitution at nucleotide position 2108, causing the lysine (K) at amino acid position 703 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Pathogenic
D
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MVP
MPC
0.79
ClinPred
T
GERP RS
Varity_R
gMVP
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