rs2607336

Variant names:

• chr19-55292452-A-C
• rs2607336
• NM_032430.2:c.459-1565A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032430.2(BRSK1):​c.459-1565A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,022 control chromosomes in the GnomAD database, including 19,088 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19088 hom., cov: 32)
• Consequence: BRSK1 NM_032430.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRSK1	NM_032430.2	c.459-1565A>C		intron_variant	Intron 4 of 18	ENST00000309383.6	NP_115806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRSK1	ENST00000309383.6	c.459-1565A>C		intron_variant	Intron 4 of 18	1	NM_032430.2	ENSP00000310649.1
BRSK1	ENST00000590333.5	c.507-1565A>C		intron_variant	Intron 6 of 20	1		ENSP00000468190.1
BRSK1	ENST00000585418.1	c.459-1565A>C		intron_variant	Intron 4 of 9	1		ENSP00000467357.1
BRSK1	ENST00000592539.6	n.*204-1565A>C		intron_variant	Intron 5 of 6	5		ENSP00000466755.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75426 AN: 151904 Hom.: 19062 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.509

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75508 AN: 152022 Hom.: 19088 Cov.: 32 AF XY: 0.494 AC XY: 36728 AN XY: 74282

African (AFR) AF: 0.508 AC: 21068 AN: 41472

American (AMR) AF: 0.452 AC: 6893 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2135 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1199 AN: 5172

South Asian (SAS) AF: 0.556 AC: 2678 AN: 4818

European-Finnish (FIN) AF: 0.509 AC: 5372 AN: 10556

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34466 AN: 67966

Other (OTH) AF: 0.512 AC: 1079 AN: 2106

Alfa AF: 0.501 Hom.: 25215

Bravo AF: 0.487

Asia WGS AF: 0.466 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.45
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2607336; hg19: chr19-55803820;