8-140703675-G-A

Position:

• chr8-140703675-G-A

Variant summary

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

The NM_001352702.2(PTK2):​c.2353-968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,078 control chromosomes in the GnomAD database, including 43,004 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 0.74 (43004 hom., cov: 32)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2	NM_001352702.2	c.2353-968C>T		intron_variant		ENST00000696786.1	NP_001339631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK2	ENST00000696786.1	c.2353-968C>T		intron_variant			NM_001352702.2	ENSP00000512868	P4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112579 AN: 151960 Hom.: 42985 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.741 AC: 112644 AN: 152078 Hom.: 43004 Cov.: 32 AF XY: 0.737 AC XY: 54782 AN XY: 74364

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.784

Alfa AF: 0.816 Hom.: 68741

Bravo AF: 0.730

Asia WGS AF: 0.580 AC: 2019 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	0.50
DANN	Benign	0.49

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: rs10109684; hg19: chr8-141713774;