16-29977620-A-T

Variant names:

• chr16-29977620-A-T
• rs4583255
• NM_016151.4:c.-35-118A>T

Variant summary

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

The NM_016151.4(TAOK2):​c.-35-118A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000123 in 814,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAOK2 NM_016151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• immunodeficiency disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• inborn error of immunity

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016151.4. 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
	TAOK2	NM_016151.4	MANE Select	c.-35-118A>T		intron	N/A	NP_057235.2
	TAOK2	NM_001252043.2		c.-35-118A>T		intron	N/A	NP_001238972.1	Q9UL54-4
	TAOK2	NM_004783.4		c.-35-118A>T		intron	N/A	NP_004774.1	Q9UL54-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAOK2	ENST00000308893.9	TSL:1 MANE Select	c.-35-118A>T		intron	N/A	ENSP00000310094.4	Q9UL54-1
	TAOK2	ENST00000543033.5	TSL:1	c.-35-118A>T		intron	N/A	ENSP00000440336.1	Q9UL54-4
	TAOK2	ENST00000279394.7	TSL:1	c.-35-118A>T		intron	N/A	ENSP00000279394.3	Q9UL54-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151850 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.00000123 AC: 1 AN: 814474 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 407910

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19118

American (AMR) AF: 0.00 AC: 0 AN: 19080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15618

East Asian (EAS) AF: 0.00 AC: 0 AN: 32622

South Asian (SAS) AF: 0.00 AC: 0 AN: 50924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2664

European-Non Finnish (NFE) AF: 0.00000165 AC: 1 AN: 605464

Other (OTH) AF: 0.00 AC: 0 AN: 37800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151850 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74142

African (AFR) AF: 0.00 AC: 0 AN: 41354

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67922

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.86
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 5

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

Other links and lift over

dbSNP: rs4583255; hg19: chr16-29988941;