8-140780382-A-C

Position:

• chr8-140780382-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001352702.2(PTK2):​c.1177+9092T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,946 control chromosomes in the GnomAD database, including 27,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (27569 hom., cov: 31)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56

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]

PTK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 8-140780382-A-C is Benign according to our data. Variant chr8-140780382-A-C is described in ClinVar as [Benign]. Clinvar id is 1266242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2	NM_001352702.2	c.1177+9092T>G		intron_variant		ENST00000696786.1	NP_001339631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK2	ENST00000696786.1	c.1177+9092T>G		intron_variant			NM_001352702.2	ENSP00000512868.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88640 AN: 151828 Hom.: 27525 Cov.: 31

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.584 AC: 88729 AN: 151946 Hom.: 27569 Cov.: 31 AF XY: 0.588 AC XY: 43634 AN XY: 74254

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.520

Alfa AF: 0.374 Hom.: 867

Bravo AF: 0.597

Asia WGS AF: 0.622 AC: 2162 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	-0.96
CADD	Benign	0.023
DANN	Benign	0.69

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: rs7843014; hg19: chr8-141790481;