chr19-55529804-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370096.2(SBK2):​c.976G>A​(p.Gly326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,222 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: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SBK2
NM_001370096.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.422
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SBK2NM_001370096.2 linkc.976G>A p.Gly326Arg missense_variant Exon 4 of 4 ENST00000413299.6 NP_001357025.1
SBK2XM_011527227.3 linkc.*535G>A 3_prime_UTR_variant Exon 4 of 4 XP_011525529.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SBK2ENST00000413299.6 linkc.976G>A p.Gly326Arg missense_variant Exon 4 of 4 5 NM_001370096.2 ENSP00000389015.2 P0C263
SBK2ENST00000344158.4 linkc.976G>A p.Gly326Arg missense_variant Exon 3 of 3 2 ENSP00000345044.3 P0C263

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000413
AC:
6
AN:
1452222
Hom.:
0
Cov.:
34
AF XY:
0.00000415
AC XY:
3
AN XY:
722870
show subpopulations
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.976G>A (p.G326R) alteration is located in exon 4 (coding exon 3) of the SBK2 gene. This alteration results from a G to A substitution at nucleotide position 976, causing the glycine (G) at amino acid position 326 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.020
T;T
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.67
T;.
M_CAP
Uncertain
0.25
D
MetaRNN
Uncertain
0.60
D;D
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.5
N;N
REVEL
Benign
0.27
Sift
Benign
0.11
T;T
Sift4G
Uncertain
0.042
D;D
Polyphen
0.99
D;D
Vest4
0.53
MutPred
0.28
Gain of MoRF binding (P = 0.0301);Gain of MoRF binding (P = 0.0301);
MVP
0.64
MPC
2.3
ClinPred
0.92
D
GERP RS
3.9
Varity_R
0.12
gMVP
0.62

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: chr19-56041171; COSMIC: COSV60013920; API