chr3-195867344-C-T

Variant names:

• chr3-195867344-C-T
• rs754379756
• NM_001382273.1:c.2937+17G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382273.1(TNK2):​c.2937+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,532 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TNK2 NM_001382273.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.850
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.2937+17G>A		intron	N/A	NP_001369202.1	A0A5F9ZGX5
	TNK2	NM_001387707.1		c.3033+17G>A		intron	N/A	NP_001374636.1
	TNK2	NM_001382272.1		c.3009+17G>A		intron	N/A	NP_001369201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK2	ENST00000672887.2	MANE Select	c.2937+17G>A		intron	N/A	ENSP00000499899.1	A0A5F9ZGX5
	TNK2	ENST00000428187.7	TSL:1	c.2988+17G>A		intron	N/A	ENSP00000392546.1	C9J1X3
	TNK2	ENST00000333602.14	TSL:1	c.2892+17G>A		intron	N/A	ENSP00000329425.6	Q07912-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455532 Hom.: 0 Cov.: 38 AF XY: 0.00000414 AC XY: 3 AN XY: 723840

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 43902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109680

Other (OTH) AF: 0.0000166 AC: 1 AN: 60106

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs754379756; hg19: chr3-195594215;