Variant rs1056749 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.2364T>C(p.Ala788=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,532,962 control chromosomes in the GnomAD database, including 22,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1885 hom., cov: 32)

Exomes 𝑓: 0.17 ( 20335 hom. )

Consequence

TNK2
NM_001382273.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.277

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-195867934-A-G is Benign according to our data. Variant chr3-195867934-A-G is described in ClinVar as [Benign]. Clinvar id is 259877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.277 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 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.2364T>C	p.Ala788=	synonymous_variant	13/16	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.2364T>C	p.Ala788=	synonymous_variant	13/16		NM_001382273.1	ENSP00000499899

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23190

AN:

151564

Hom.:

1887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0448

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.106

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.143

AC:

22033

AN:

154566

Hom.:

1707

AF XY:

0.145

AC XY:

12464

AN XY:

85960

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.0787

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.0504

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.168

AC:

232537

AN:

1381278

Hom.:

20335

Cov.:

AF XY:

0.167

AC XY:

114204

AN XY:

682540

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0825

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.0667

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.153

AC:

23184

AN:

151684

Hom.:

1885

Cov.:

AF XY:

0.150

AC XY:

11159

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.0446

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.160

Hom.:

460

Bravo

AF:

0.152

Asia WGS

AF:

0.0860

AC:

300

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 31, 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

-0.89

CADD

Benign

6.6

DANN

Benign

0.40

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

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