8-140955682-G-T

Position:

• chr8-140955682-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.-121-29933C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,924 control chromosomes in the GnomAD database, including 15,172 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 0.42 (15172 hom., cov: 32)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2	NM_001352702.2	c.-121-29933C>A		intron_variant		ENST00000696786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2	ENST00000696786.1	c.-121-29933C>A		intron_variant			NM_001352702.2	P4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63451 AN: 151804 Hom.: 15163 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.418 AC: 63480 AN: 151924 Hom.: 15172 Cov.: 32 AF XY: 0.414 AC XY: 30739 AN XY: 74258

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.491

Alfa AF: 0.489 Hom.: 8013

Bravo AF: 0.405

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.54

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: rs1375062; hg19: chr8-141965781;