16-29978107-A-G

Position:

• chr16-29978107-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_016151.4(TAOK2):​c.151A>G​(p.Ser51Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: TAOK2 NM_016151.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

Genes affected

TAOK2 (HGNC:16835): (TAO kinase 2) Enables mitogen-activated protein kinase kinase binding activity; neuropilin binding activity; and protein serine/threonine kinase activity. Involved in several processes, including focal adhesion assembly; intracellular signal transduction; and positive regulation of JNK cascade. Located in cytoplasmic vesicle; cytosol; and nuclear lumen. Part of receptor complex. [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
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TAOK2. . Gene score misZ 3.2101 (greater than the threshold 3.09). Trascript score misZ 3.3599 (greater than threshold 3.09). GenCC has associacion of gene with autism spectrum disorder, immunodeficiency disease.
• BP4: Computational evidence support a benign effect (MetaRNN=0.113076806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK2	NM_016151.4	c.151A>G	p.Ser51Gly	missense_variant	3/16	ENST00000308893.9	NP_057235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK2	ENST00000308893.9	c.151A>G	p.Ser51Gly	missense_variant	3/16	1	NM_016151.4	ENSP00000310094.4
TAOK2	ENST00000543033.5	c.151A>G	p.Ser51Gly	missense_variant	3/17	1		ENSP00000440336.1
TAOK2	ENST00000279394.7	c.151A>G	p.Ser51Gly	missense_variant	3/19	1		ENSP00000279394.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 18, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TAOK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 51 of the TAOK2 protein (p.Ser51Gly). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.027
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.016	B;.;B
Vest4		0.33
MutPred		0.38		Loss of phosphorylation at S51 (P = 0.0891);Loss of phosphorylation at S51 (P = 0.0891);Loss of phosphorylation at S51 (P = 0.0891);
MVP		0.38
MPC		1.0
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr16-29989428;