8-140658761-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001352702.2(PTK2):c.*705T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 221,350 control chromosomes in the GnomAD database, including 20,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12839 hom., cov: 32)
  • Exomes 𝑓: 0.46 (7675 hom.)
• Consequence: PTK2 NM_001352702.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.831

Genes affected

PTK2 (HGNC:9611): (protein tyrosine kinase 2) This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 8-140658761-A-T is Benign according to our data. Variant chr8-140658761-A-T is described in ClinVar as [Benign]. Clinvar id is 1226102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2	NM_001352702.2	c.*705T>A		3_prime_UTR_variant	36/36	ENST00000696786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2	ENST00000696786.1	c.*705T>A		3_prime_UTR_variant	36/36		NM_001352702.2	P4

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59043 AN: 151950 Hom.: 12828 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.460 AC: 31872 AN: 69282 Hom.: 7675 Cov.: 0 AF XY: 0.469 AC XY: 15027 AN XY: 32052

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.464

GnomAD4 genome AF: 0.388 AC: 59065 AN: 152068 Hom.: 12839 Cov.: 32 AF XY: 0.388 AC XY: 28812 AN XY: 74314

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.457

Alfa AF: 0.302 Hom.: 880

Bravo AF: 0.379

Asia WGS AF: 0.392 AC: 1367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 24930376) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	6.8
Dann	Benign	0.80

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: rs7460; hg19: chr8-141668860;