19-55306391-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_032430.2(BRSK1):c.2030C>T(p.Pro677Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000843 in 1,613,968 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
BRSK1
NM_032430.2 missense
NM_032430.2 missense
Scores
1
3
10
Clinical Significance
Conservation
PhyloP100: 3.63
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 -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, BRSK1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24834535).
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRSK1 | NM_032430.2 | c.2030C>T | p.Pro677Leu | missense_variant | 17/19 | ENST00000309383.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRSK1 | ENST00000309383.6 | c.2030C>T | p.Pro677Leu | missense_variant | 17/19 | 1 | NM_032430.2 | P1 | |
BRSK1 | ENST00000590333.5 | c.2078C>T | p.Pro693Leu | missense_variant | 19/21 | 1 | |||
BRSK1 | ENST00000326848.7 | c.1115C>T | p.Pro372Leu | missense_variant | 9/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251128Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135792
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GnomAD4 exome AF: 0.0000883 AC: 129AN: 1461646Hom.: 0 Cov.: 32 AF XY: 0.0000798 AC XY: 58AN XY: 727154
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74490
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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 | Jun 18, 2021 | The c.2030C>T (p.P677L) alteration is located in exon 17 (coding exon 17) of the BRSK1 gene. This alteration results from a C to T substitution at nucleotide position 2030, causing the proline (P) at amino acid position 677 to be replaced by a leucine (L). 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
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MutPred
0.13
.;Loss of glycosylation at P677 (P = 0.0218);.;
MVP
MPC
1.1
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