8-140700903-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001352702.2(PTK2):c.2610G>A(p.Glu870=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,613,814 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (5 hom.)
• Consequence: PTK2 NM_001352702.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.396

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 8-140700903-C-T is Benign according to our data. Variant chr8-140700903-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 787622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.
• BS2: High AC in GnomAd at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2	NM_001352702.2	c.2610G>A	p.Glu870=	synonymous_variant	29/36	ENST00000696786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2	ENST00000696786.1	c.2610G>A	p.Glu870=	synonymous_variant	29/36		NM_001352702.2	P4

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 265 AN: 152098 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00179 AC: 449 AN: 251292 Hom.: 0 AF XY: 0.00184 AC XY: 250 AN XY: 135828

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00282

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00310 AC: 4532 AN: 1461598 Hom.: 5 Cov.: 30 AF XY: 0.00300 AC XY: 2178 AN XY: 727124

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.000543

Gnomad4 NFE exome AF: 0.00372

Gnomad4 OTH exome AF: 0.00290

GnomAD4 genome AF: 0.00174 AC: 265 AN: 152216 Hom.: 1 Cov.: 32 AF XY: 0.00173 AC XY: 129 AN XY: 74414

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00306

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00255 Hom.: 0

Bravo AF: 0.00191

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00245

EpiControl AF: 0.00332

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	PTK2: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Aug 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	7.6
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: rs140437945; hg19: chr8-141711002;