chr11-1436037-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 28. This position FAILED quality control check.

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

GnomAD2 exomes

AF:

0.00191

AC:

454

AN:

237902

AF XY:

0.00240

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 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

AC:

AN:

33264

Gnomad4 AMR exome

AF:

0.00171

AC:

AN:

43796

Gnomad4 ASJ exome

AF:

0.000232

AC:

AN:

25832

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39222

Gnomad4 SAS exome

AF:

0.00981

AC:

829

AN:

84468

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52062

Gnomad4 NFE exome

AF:

0.000540

AC:

598

AN:

1107698

Gnomad4 Remaining exome

AF:

0.00192

AC:

115

AN:

60006

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.000169475

AN:

0.000169475

Gnomad4 AMR

AF:

0.00249

AC:

0.00249475

AN:

0.00249475

Gnomad4 ASJ

AF:

0.000577

AC:

0.000576701

AN:

0.000576701

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00836

AC:

0.00835771

AN:

0.00835771

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000766

AC:

0.000766284

AN:

0.000766284

Gnomad4 OTH

AF:

0.00381

AC:

0.00380952

AN:

0.00380952

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BRSK2: BP4, BS2 -

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BRSK2-related disorder

Benign:1

Aug 17, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Mutation Taster

=99/1

polymorphism

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