Variant chr11-1436037-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001256627.2(BRSK2):c.92-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00115 in 1,603,538 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0012 ( 15 hom. )

Consequence

BRSK2
NM_001256627.2 splice_region, intron

Scores

Splicing: ADA: 0.07717

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.49

Variant links:

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]

BRSK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 11-1436037-C-T is Benign according to our data. Variant chr11-1436037-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 720380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000976 (148/151610) while in subpopulation SAS AF= 0.00836 (40/4786). AF 95% confidence interval is 0.00631. There are 0 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRSK2	NM_001256627.2 link	c.92-3C>T		splice_region_variant, intron_variant	Intron 1 of 19	ENST00000528841.6	NP_001243556.1	Q8IWQ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRSK2	ENST00000528841.6 link	c.92-3C>T		splice_region_variant, intron_variant	Intron 1 of 19	1	NM_001256627.2	ENSP00000432000.1		Q8IWQ3-1

Frequencies

GnomAD3 genomes

AF:

0.000984

AC:

149

AN:

151490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00835

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000766

Gnomad OTH

AF:

0.00385

GnomAD3 exomes

AF:

0.00191

AC:

454

AN:

237902

Hom.:

AF XY:

0.00240

AC XY:

311

AN XY:

129500

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.000513

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00964

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000994

Gnomad OTH exome

AF:

0.00225

GnomAD4 exome

AF:

0.00116

AC:

1690

AN:

1451928

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1050

AN XY:

721754

show subpopulations

Gnomad4 AFR exome

AF:

0.000271

Gnomad4 AMR exome

AF:

0.00171

Gnomad4 ASJ exome

AF:

0.000232

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00981

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000540

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.000976

AC:

148

AN:

151610

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

AN XY:

74072

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00249

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00836

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000766

Gnomad4 OTH

AF:

0.00381

Alfa

AF:

0.000884

Hom.:

Bravo

AF:

0.00105

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2024	BRSK2: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

BRSK2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 17, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.077

dbscSNV1_RF

Benign

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over