rs1056749

chr3-195867934-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.277

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]

ACMG classification

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	UniProt
TNK2	NM_001382273.1	c.2364T>C	p.Ala788=	synonymous_variant	13/16	ENST00000672887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNK2	ENST00000672887.2	c.2364T>C	p.Ala788=	synonymous_variant	13/16		NM_001382273.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23190 AN: 151564 Hom.: 1887 Cov.: 32

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

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.: 50 AF XY: 0.167 AC XY: 114204 AN XY: 682540

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.: 32 AF XY: 0.150 AC XY: 11159 AN XY: 74148

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

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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

Other links and lift over

dbSNP: rs1056749; hg19: chr3-195594805; COSMIC: COSV57365543; COSMIC: COSV57365543;