16-29977795-G-C

Position:

• chr16-29977795-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_016151.4(TAOK2):​c.23G>C​(p.Gly8Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 10.0

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 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK2	NM_016151.4	c.23G>C	p.Gly8Ala	missense_variant	2/16	ENST00000308893.9	NP_057235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAOK2	ENST00000308893.9	c.23G>C	p.Gly8Ala	missense_variant	2/16	1	NM_016151.4	ENSP00000310094.4
TAOK2	ENST00000543033.5	c.23G>C	p.Gly8Ala	missense_variant	2/17	1		ENSP00000440336.1
TAOK2	ENST00000279394.7	c.23G>C	p.Gly8Ala	missense_variant	2/19	1		ENSP00000279394.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 09, 2021

This sequence change replaces glycine with alanine at codon 8 of the TAOK2 protein (p.Gly8Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals affected with TAOK2-related conditions. This variant is not present in population databases (ExAC no frequency). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.97	L;L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.023	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.55	P;.;D
Vest4		0.65
MutPred		0.20		Loss of methylation at R6 (P = 0.1463);Loss of methylation at R6 (P = 0.1463);Loss of methylation at R6 (P = 0.1463);
MVP		0.84
MPC		1.5
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.68
gMVP		0.70

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: chr16-29989116;