Variant rs3761718 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382273.1(TNK2):c.915C>T(p.Arg305Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,613,780 control chromosomes in the GnomAD database, including 2,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 235 hom., cov: 32)

Exomes 𝑓: 0.017 ( 2005 hom. )

Consequence

TNK2
NM_001382273.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.846

Variant links:

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 links:

TNK2 (HGNC:):

TNK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-195879148-G-A is Benign according to our data. Variant chr3-195879148-G-A is described in ClinVar as [Benign]. Clinvar id is 259883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.846 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNK2	NM_001382273.1 linkuse as main transcript	c.915C>T	p.Arg305Arg	synonymous_variant	7/16	ENST00000672887.2	NP_001369202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNK2	ENST00000672887.2 linkuse as main transcript	c.915C>T	p.Arg305Arg	synonymous_variant	7/16		NM_001382273.1	ENSP00000499899.1		A0A5F9ZGX5

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3070

AN:

152146

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0560

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.0794

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0415

AC:

10428

AN:

251052

Hom.:

850

AF XY:

0.0410

AC XY:

5562

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.0706

Gnomad ASJ exome

AF:

0.00665

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.0747

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.00287

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0166

AC:

24315

AN:

1461514

Hom.:

2005

Cov.:

AF XY:

0.0180

AC XY:

13108

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.0670

Gnomad4 ASJ exome

AF:

0.00643

Gnomad4 EAS exome

AF:

0.271

Gnomad4 SAS exome

AF:

0.0738

Gnomad4 FIN exome

AF:

0.0150

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.0240

GnomAD4 genome

AF:

0.0202

AC:

3069

AN:

152266

Hom.:

235

Cov.:

AF XY:

0.0239

AC XY:

1780

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00351

Gnomad4 AMR

AF:

0.0558

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.0796

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.0224

Asia WGS

AF:

0.150

AC:

521

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.1

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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