TNK2 p.Ile343Ile

Variant names:

• chr3-195878577-C-C
• NM_001382273.1:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-195878578--
• chr3-195878578-G-A
• chr3-195878578-G-T

Variant summary

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

The NM_001382273.1(TNK2):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TNK2 NM_001382273.1 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 0 publications found

Genes affected

TNK2 (HGNC:19297): (tyrosine kinase non receptor 2) This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

TNK2 Gene-Disease associations (from GenCC):

• infantile-onset mesial temporal lobe epilepsy with severe cognitive regression

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• genetic generalized epilepsy

  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_001382273.1. 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
	TNK2	NM_001382273.1	MANE Select	c.		exon_region	Exon 8 of 16	NP_001369202.1	A0A5F9ZGX5
	TNK2	NM_001387707.1		c.		exon_region	Exon 8 of 16	NP_001374636.1
	TNK2	NM_001382272.1		c.		exon_region	Exon 8 of 16	NP_001369201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK2	ENST00000672887.2	MANE Select	c.		exon_region	Exon 8 of 16	ENSP00000499899.1	A0A5F9ZGX5
	TNK2	ENST00000428187.7	TSL:1	c.		exon_region	Exon 8 of 14	ENSP00000392546.1	C9J1X3
	TNK2	ENST00000333602.14	TSL:1	c.		exon_region	Exon 8 of 15	ENSP00000329425.6	Q07912-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.81

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-195605448;