rs1056726

Variant names:

• chr3-195868534-G-A
• rs1056726
• NM_001382273.1:c.1764C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-195868534-G-A
• chr3-195868534-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The NM_001382273.1(TNK2):​c.1764C>T​(p.Phe588Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 1,564,262 control chromosomes in the GnomAD database, including 3,206 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (332 hom., cov: 33)
  • Exomes 𝑓: 0.061 (2874 hom.)
• Consequence: TNK2 NM_001382273.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.821
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• infantile-onset mesial temporal lobe epilepsy with severe cognitive regression

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• genetic generalized epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant 3-195868534-G-A is Benign according to our data. Variant chr3-195868534-G-A is described in ClinVar as Benign. ClinVar VariationId is 259872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.821 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382273.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK2	NM_001382273.1	MANE Select	c.1764C>T	p.Phe588Phe	synonymous	Exon 13 of 16	NP_001369202.1	A0A5F9ZGX5
	TNK2	NM_001387707.1		c.1860C>T	p.Phe620Phe	synonymous	Exon 13 of 16	NP_001374636.1
	TNK2	NM_001382272.1		c.1836C>T	p.Phe612Phe	synonymous	Exon 13 of 16	NP_001369201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNK2	ENST00000672887.2	MANE Select	c.1764C>T	p.Phe588Phe	synonymous	Exon 13 of 16	ENSP00000499899.1	A0A5F9ZGX5
	TNK2	ENST00000428187.7	TSL:1	c.1815C>T	p.Phe605Phe	synonymous	Exon 12 of 14	ENSP00000392546.1	C9J1X3
	TNK2	ENST00000333602.14	TSL:1	c.1719C>T	p.Phe573Phe	synonymous	Exon 12 of 15	ENSP00000329425.6	Q07912-1

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9231 AN: 152090 Hom.: 332 Cov.: 33

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0468

GnomAD2 exomes AF: 0.0544 AC: 9235 AN: 169668 AF XY: 0.0553

Gnomad AFR exome AF: 0.0894

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0260

Gnomad EAS exome AF: 0.0831

Gnomad FIN exome AF: 0.0351

Gnomad NFE exome AF: 0.0594

Gnomad OTH exome AF: 0.0498

GnomAD4 exome AF: 0.0610 AC: 86078 AN: 1412054 Hom.: 2874 Cov.: 45 AF XY: 0.0609 AC XY: 42674 AN XY: 701090

African (AFR) AF: 0.0899 AC: 2880 AN: 32048

American (AMR) AF: 0.0214 AC: 805 AN: 37588

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 648 AN: 25220

East Asian (EAS) AF: 0.109 AC: 4098 AN: 37696

South Asian (SAS) AF: 0.0691 AC: 5727 AN: 82850

European-Finnish (FIN) AF: 0.0380 AC: 1402 AN: 36880

Middle Eastern (MID) AF: 0.0595 AC: 313 AN: 5262

European-Non Finnish (NFE) AF: 0.0609 AC: 66784 AN: 1095854

Other (OTH) AF: 0.0583 AC: 3421 AN: 58656

GnomAD4 genome AF: 0.0607 AC: 9242 AN: 152208 Hom.: 332 Cov.: 33 AF XY: 0.0602 AC XY: 4479 AN XY: 74408

African (AFR) AF: 0.0848 AC: 3520 AN: 41518

American (AMR) AF: 0.0321 AC: 492 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.0802 AC: 414 AN: 5162

South Asian (SAS) AF: 0.0612 AC: 296 AN: 4834

European-Finnish (FIN) AF: 0.0357 AC: 379 AN: 10622

Middle Eastern (MID) AF: 0.0345 AC: 10 AN: 290

European-Non Finnish (NFE) AF: 0.0571 AC: 3884 AN: 67978

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0542 Hom.: 65

Bravo AF: 0.0632

Asia WGS AF: 0.0710 AC: 247 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.15
DANN	Benign	0.68
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1056726; hg19: chr3-195595405; COSMIC: COSV57368889; COSMIC: COSV57368889;