NM_001256627.2:c.62T>A

Variant names:

• chr11-1390346-T-A
• NM_001256627.2:c.62T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001256627.2(BRSK2):​c.62T>A​(p.Leu21Gln) variant causes a missense 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRSK2 NM_001256627.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0340

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4209002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRSK2	NM_001256627.2	c.62T>A	p.Leu21Gln	missense_variant	Exon 1 of 20	ENST00000528841.6	NP_001243556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRSK2	ENST00000528841.6	c.62T>A	p.Leu21Gln	missense_variant	Exon 1 of 20	1	NM_001256627.2	ENSP00000432000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 893410 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 416742

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Apr 26, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.068
FATHMM_MKL	Benign	0.25	N
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.7	M;M;M;M
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.32
MVP		0.67
ClinPred		0.98	D
GERP RS		1.5
Varity_R		0.78

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: chr11-1411576;