Variant 8-140668316-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001352702.2(PTK2):c.2950A>G(p.Ser984Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000394 in 1,614,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

PTK2
NM_001352702.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

Variant links:

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 links:

PTK2 (HGNC:):

PTK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041706145).

BS2

High AC in GnomAd4 at 101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2	NM_001352702.2 linkuse as main transcript	c.2950A>G	p.Ser984Gly	missense_variant	34/36	ENST00000696786.1	NP_001339631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK2	ENST00000696786.1 linkuse as main transcript	c.2950A>G	p.Ser984Gly	missense_variant	34/36		NM_001352702.2	ENSP00000512868.1		A0A8Q3WLM4

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000354

AC:

AN:

251436

Hom.:

AF XY:

0.000434

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000366

AC:

535

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

282

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000402

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152296

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.000737

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.2884A>G (p.S962G) alteration is located in exon 30 (coding exon 29) of the PTK2 gene. This alteration results from a A to G substitution at nucleotide position 2884, causing the serine (S) at amino acid position 962 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;.;T;T;T;.;.;.;T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.99

.;D;D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.042

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;.;L;.;.;.;.;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

N;.;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.039

D;.;T;T;D;T;T;D;T;T;D

Sift4G

Benign

0.068

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.69

P;.;P;.;P;.;.;.;.;.;.

Vest4

0.40

MVP

0.37

MPC

0.70

ClinPred

0.088

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over