Genetic Variant SBK2:p.Gly326Arg (chr19-55529804-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001370096.2(SBK2):c.976G>C(p.Gly326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,604,356 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

SBK2
NM_001370096.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.422

Publications

0 publications found

Variant links:

Genes affected

SBK2 (HGNC:34416): (SH3 domain binding kinase family member 2) Predicted to enable MAP kinase kinase activity. Predicted to be involved in MAPK cascade and protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

SBK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370096.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBK2	NM_001370096.2	MANE Select	c.976G>C	p.Gly326Arg	missense	Exon 4 of 4	NP_001357025.1	P0C263

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SBK2	ENST00000413299.6	TSL:5 MANE Select	c.976G>C	p.Gly326Arg	missense	Exon 4 of 4	ENSP00000389015.2	P0C263
SBK2	ENST00000344158.4	TSL:2	c.976G>C	p.Gly326Arg	missense	Exon 3 of 3	ENSP00000345044.3	P0C263
SBK2	ENST00000912390.1		c.976G>C	p.Gly326Arg	missense	Exon 4 of 4	ENSP00000582449.1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000109

AC:

AN:

229214

AF XY:

0.000110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.000300

AC:

436

AN:

1452222

Hom.:

Cov.:

AF XY:

0.000302

AC XY:

218

AN XY:

722870

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000364

AC:

405

AN:

1111654

Other (OTH)

AF:

0.000481

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000125

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41450

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.000247

Hom.:

Bravo

AF:

0.000181

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000246

AC:

ESP6500EA

AF:

0.000360

AC:

ExAC

AF:

0.0000832

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.24

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.3

PhyloP100

0.42

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.28

Sift

Benign

0.11

Sift4G

Uncertain

0.042

Polyphen

0.99

Vest4

0.53

MutPred

0.28

Gain of MoRF binding (P = 0.0301)

MVP

0.64

MPC

2.3

ClinPred

0.16

GERP RS

3.9

Varity_R

0.12

gMVP

0.62

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over