3-195868090-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001382273.1(TNK2):c.2208G>A(p.Pro736=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 1,610,118 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0096 (114 hom.)
• Consequence: TNK2 NM_001382273.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.97

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-195868090-C-T is Benign according to our data. Variant chr3-195868090-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-195868090-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-5.97 with no splicing effect.
• BS2: High AC in GnomAd at 920 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNK2	NM_001382273.1	c.2208G>A	p.Pro736=	synonymous_variant	13/16	ENST00000672887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNK2	ENST00000672887.2	c.2208G>A	p.Pro736=	synonymous_variant	13/16		NM_001382273.1

Frequencies

GnomAD3 genomes AF: 0.00605 AC: 920 AN: 151996 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00883

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00727 AC: 1711 AN: 235278 Hom.: 19 AF XY: 0.00738 AC XY: 955 AN XY: 129396

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00571

Gnomad FIN exome AF: 0.0163

Gnomad NFE exome AF: 0.00950

Gnomad OTH exome AF: 0.00686

GnomAD4 exome AF: 0.00955 AC: 13931 AN: 1458004 Hom.: 114 Cov.: 52 AF XY: 0.00946 AC XY: 6859 AN XY: 725236

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00178

Gnomad4 ASJ exome AF: 0.00887

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00633

Gnomad4 FIN exome AF: 0.0143

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.00605 AC: 920 AN: 152114 Hom.: 4 Cov.: 33 AF XY: 0.00637 AC XY: 474 AN XY: 74380

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.00883

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00800 Hom.: 2

Bravo AF: 0.00524

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.0090
Dann	Benign	0.52

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: rs62283329; hg19: chr3-195594961;