3-195867379-T-C

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.2919A>G(p.Pro973=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000418 in 1,604,876 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (3 hom.)
• Consequence: TNK2 NM_001382273.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19

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=-1.0).
• BP6: Variant 3-195867379-T-C is Benign according to our data. Variant chr3-195867379-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2654500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS2: High AC in GnomAd at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNK2	NM_001382273.1	c.2919A>G	p.Pro973=	synonymous_variant	13/16	ENST00000672887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNK2	ENST00000672887.2	c.2919A>G	p.Pro973=	synonymous_variant	13/16		NM_001382273.1

Frequencies

GnomAD3 genomes AF: 0.000328 AC: 50 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000440 AC: 98 AN: 222630 Hom.: 0 AF XY: 0.000514 AC XY: 63 AN XY: 122600

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000366

Gnomad ASJ exome AF: 0.000427

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000780

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000532

Gnomad OTH exome AF: 0.00128

GnomAD4 exome AF: 0.000428 AC: 621 AN: 1452544 Hom.: 3 Cov.: 38 AF XY: 0.000455 AC XY: 329 AN XY: 722362

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000343

Gnomad4 ASJ exome AF: 0.000425

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000332

Gnomad4 OTH exome AF: 0.000783

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000295 AC XY: 22 AN XY: 74488

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000496 Hom.: 0

Bravo AF: 0.000306

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	TNK2: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	May 12, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.011
Dann	Benign	0.25

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: rs373134167; hg19: chr3-195594250;