chr3-195870036-T-C

Variant names:

• chr3-195870036-T-C
• rs2278034
• NM_001382273.1:c.1543+78A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382273.1(TNK2):​c.1543+78A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,104,746 control chromosomes in the GnomAD database, including 151,154 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16849 hom., cov: 32)
  • Exomes 𝑓: 0.52 (134305 hom.)
• Consequence: TNK2 NM_001382273.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 18 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNK2	NM_001382273.1	c.1543+78A>G		intron_variant	Intron 11 of 15	ENST00000672887.2	NP_001369202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNK2	ENST00000672887.2	c.1543+78A>G		intron_variant	Intron 11 of 15		NM_001382273.1	ENSP00000499899.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69420 AN: 151844 Hom.: 16845 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.484

GnomAD2 exomes AF: 0.443 AC: 33030 AN: 74544 AF XY: 0.442

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.560

Gnomad OTH exome AF: 0.483

GnomAD4 exome AF: 0.520 AC: 495558 AN: 952784 Hom.: 134305 Cov.: 12 AF XY: 0.516 AC XY: 242671 AN XY: 470306

African (AFR) AF: 0.337 AC: 7355 AN: 21812

American (AMR) AF: 0.421 AC: 7668 AN: 18200

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 8862 AN: 16338

East Asian (EAS) AF: 0.172 AC: 5605 AN: 32494

South Asian (SAS) AF: 0.359 AC: 19100 AN: 53220

European-Finnish (FIN) AF: 0.494 AC: 21673 AN: 43876

Middle Eastern (MID) AF: 0.508 AC: 2297 AN: 4522

European-Non Finnish (NFE) AF: 0.558 AC: 401710 AN: 720468

Other (OTH) AF: 0.509 AC: 21288 AN: 41854

GnomAD4 genome AF: 0.457 AC: 69467 AN: 151962 Hom.: 16849 Cov.: 32 AF XY: 0.450 AC XY: 33412 AN XY: 74292

African (AFR) AF: 0.336 AC: 13925 AN: 41418

American (AMR) AF: 0.437 AC: 6678 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1876 AN: 3470

East Asian (EAS) AF: 0.155 AC: 802 AN: 5176

South Asian (SAS) AF: 0.349 AC: 1684 AN: 4820

European-Finnish (FIN) AF: 0.487 AC: 5152 AN: 10570

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.556 AC: 37744 AN: 67914

Other (OTH) AF: 0.482 AC: 1017 AN: 2110

Alfa AF: 0.534 Hom.: 33939

Bravo AF: 0.449

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.24
PhyloP100		0.014
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: rs2278034; hg19: chr3-195596907; COSMIC: COSV57369852; COSMIC: COSV57369852;