19-55529973-C-G

Variant names:

• chr19-55529973-C-G
• rs1268735425
• NM_001370096.2:c.807G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370096.2(SBK2):​c.807G>C​(p.Glu269Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBK2 NM_001370096.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.39
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07367933).

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.807G>C	p.Glu269Asp	missense	Exon 4 of 4	NP_001357025.1	P0C263

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBK2	ENST00000413299.6	TSL:5 MANE Select	c.807G>C	p.Glu269Asp	missense	Exon 4 of 4	ENSP00000389015.2	P0C263
	SBK2	ENST00000344158.4	TSL:2	c.807G>C	p.Glu269Asp	missense	Exon 3 of 3	ENSP00000345044.3	P0C263
	SBK2	ENST00000912390.1		c.807G>C	p.Glu269Asp	missense	Exon 4 of 4	ENSP00000582449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.8
DANN	Benign	0.55
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N
PhyloP100		-1.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.049
Sift	Benign	0.55	T
Sift4G	Benign	0.60	T
Polyphen		0.0050	B
Vest4		0.15
MutPred		0.37		Gain of helix (P = 0.2059)
MVP		0.36
MPC		0.90
ClinPred		0.015	T
GERP RS		-0.012
Varity_R		0.074
gMVP		0.38
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1268735425; hg19: chr19-56041340;