chr11-1411585-C-T

Position:

• chr11-1411585-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256627.2(BRSK2):​c.91+21210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRSK2 NM_001256627.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.11

Genes affected

BRSK2 (HGNC:11405): (BR serine/threonine kinase 2) Enables several functions, including ATP binding activity; ATPase binding activity; and protein kinase activity. Involved in several processes, including cellular protein metabolic process; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; and regulation of insulin secretion involved in cellular response to glucose stimulus. Located in centrosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05934581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRSK2	NM_001256627.2	c.91+21210C>T		intron_variant		ENST00000528841.6	NP_001243556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRSK2	ENST00000528841.6	c.91+21210C>T		intron_variant		1	NM_001256627.2	ENSP00000432000	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

BRSK2-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 22, 2023

The BRSK2 c.181C>T variant is predicted to result in the amino acid substitution p.His61Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.3
DANN	Benign	0.21
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.018
Sift	Benign	0.79	T
Sift4G	Benign	0.24	T
Polyphen		0.010	B
Vest4		0.16
MutPred		0.37		Loss of disorder (P = 0.0172);
MVP		0.41
MPC		0.015
ClinPred		0.048	T
GERP RS		-1.9
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-1432815;