16-29977812-G-A

Position:

chr16-29977812-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_016151.4(TAOK2):c.40G>A(p.Asp14Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TAOK2
NM_016151.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

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]

TAOK2 links:

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;

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=0.27874693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAOK2	NM_016151.4 linkuse as main transcript	c.40G>A	p.Asp14Asn	missense_variant	2/16	ENST00000308893.9	NP_057235.2	Q9UL54-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAOK2	ENST00000308893.9 linkuse as main transcript	c.40G>A	p.Asp14Asn	missense_variant	2/16	1	NM_016151.4	ENSP00000310094.4	Q9UL54-1
TAOK2	ENST00000543033.5 linkuse as main transcript	c.40G>A	p.Asp14Asn	missense_variant	2/17	1		ENSP00000440336.1	Q9UL54-4
TAOK2	ENST00000279394.7 linkuse as main transcript	c.40G>A	p.Asp14Asn	missense_variant	2/19	1		ENSP00000279394.3	Q9UL54-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 04, 2022

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 14 of the TAOK2 protein (p.Asp14Asn). 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 C0"). 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. This variant has not been reported in the literature in individuals affected with TAOK2-related conditions. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;.

Eigen

Benign

0.085

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.69

N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.053

T;D;T

Sift4G

Uncertain

0.060

T;T;T

Polyphen

0.018

B;.;B

Vest4

0.22

MutPred

0.27

Loss of disorder (P = 0.068);Loss of disorder (P = 0.068);Loss of disorder (P = 0.068);

MVP

0.80

MPC

1.1

ClinPred

0.90

GERP RS

5.3

Varity_R

0.17

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over