rs1868280

chr8-140886155-G-Achr8-140886155-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352702.2(PTK2):c.195+4388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,994 control chromosomes in the GnomAD database, including 14,728 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 0.41 (14728 hom., cov: 31)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2	NM_001352702.2	c.195+4388C>T		intron_variant		ENST00000696786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2	ENST00000696786.1	c.195+4388C>T		intron_variant			NM_001352702.2	P4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62461 AN: 151876 Hom.: 14718 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.475

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.411 AC: 62489 AN: 151994 Hom.: 14728 Cov.: 31 AF XY: 0.408 AC XY: 30279 AN XY: 74276

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.482

Alfa AF: 0.510 Hom.: 15075

Bravo AF: 0.398

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.3
Dann	Benign	0.76

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: rs1868280; hg19: chr8-141896254;