19-55529969-C-T

Variant names:

• chr19-55529969-C-T
• NM_001370096.2:c.811G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370096.2(SBK2):​c.811G>A​(p.Asp271Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,375,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000015 (0 hom.)
• Consequence: SBK2 NM_001370096.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36537322).

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.811G>A	p.Asp271Asn	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.811G>A	p.Asp271Asn	missense	Exon 4 of 4	ENSP00000389015.2	P0C263
	SBK2	ENST00000344158.4	TSL:2	c.811G>A	p.Asp271Asn	missense	Exon 3 of 3	ENSP00000345044.3	P0C263
	SBK2	ENST00000912390.1		c.811G>A	p.Asp271Asn	missense	Exon 4 of 4	ENSP00000582449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1375594 Hom.: 0 Cov.: 34 AF XY: 0.00000147 AC XY: 1 AN XY: 678048

African (AFR) AF: 0.00 AC: 0 AN: 29910

American (AMR) AF: 0.00 AC: 0 AN: 31154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23432

East Asian (EAS) AF: 0.00 AC: 0 AN: 35238

South Asian (SAS) AF: 0.00 AC: 0 AN: 77358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4866

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1071540

Other (OTH) AF: 0.00 AC: 0 AN: 56784

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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.46		Loss of phosphorylation at Y274 (P = 0.0854)
MVP		0.66
MPC		2.1
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.70
gMVP		0.52
Mutation Taster		=78/22	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

hg19: chr19-56041336; COSMIC: COSV106510476;