3-195868090-C-T

Variant names:

• chr3-195868090-C-T
• rs62283329
• NM_001382273.1:c.2208G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001382273.1(TNK2):​c.2208G>A​(p.Pro736Pro) 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:3
• Conservation: PhyloP100: -5.97
• Publications: 1 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.

• 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 Benign/Likely_benign. ClinVar VariationId is 259875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.97 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.2208G>A	p.Pro736Pro	synonymous	Exon 13 of 16	NP_001369202.1	A0A5F9ZGX5
	TNK2	NM_001387707.1		c.2304G>A	p.Pro768Pro	synonymous	Exon 13 of 16	NP_001374636.1
	TNK2	NM_001382272.1		c.2280G>A	p.Pro760Pro	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.2208G>A	p.Pro736Pro	synonymous	Exon 13 of 16	ENSP00000499899.1	A0A5F9ZGX5
	TNK2	ENST00000428187.7	TSL:1	c.2259G>A	p.Pro753Pro	synonymous	Exon 12 of 14	ENSP00000392546.1	C9J1X3
	TNK2	ENST00000333602.14	TSL:1	c.2163G>A	p.Pro721Pro	synonymous	Exon 12 of 15	ENSP00000329425.6	Q07912-1

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

GnomAD2 exomes AF: 0.00727 AC: 1711 AN: 235278 AF XY: 0.00738

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 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

African (AFR) AF: 0.00155 AC: 52 AN: 33448

American (AMR) AF: 0.00178 AC: 79 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00887 AC: 231 AN: 26036

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39640

South Asian (SAS) AF: 0.00633 AC: 544 AN: 85980

European-Finnish (FIN) AF: 0.0143 AC: 731 AN: 51270

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5760

European-Non Finnish (NFE) AF: 0.0104 AC: 11607 AN: 1111122

Other (OTH) AF: 0.0113 AC: 679 AN: 60250

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

African (AFR) AF: 0.00147 AC: 61 AN: 41500

American (AMR) AF: 0.00301 AC: 46 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4826

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00883 AC: 600 AN: 67942

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00800 Hom.: 2

Bravo AF: 0.00524

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.90
CADD	Benign	0.0090
DANN	Benign	0.52
PhyloP100		-6.0
Mutation Taster		=100/0	polymorphism

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: rs62283329; hg19: chr3-195594961;