8-140659629-T-C

Position:

chr8-140659629-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001352702.2(PTK2):c.3128A>G(p.Asn1043Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,614,218 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

PTK2
NM_001352702.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0980

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015859634).

BP6

Variant 8-140659629-T-C is Benign according to our data. Variant chr8-140659629-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2512796.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2	NM_001352702.2 linkuse as main transcript	c.3128A>G	p.Asn1043Ser	missense_variant	36/36	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.3128A>G	p.Asn1043Ser	missense_variant	36/36		NM_001352702.2	ENSP00000512868.1		A0A8Q3WLM4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000199

AC:

AN:

251398

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000103

AC:

151

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

102

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00150

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000844

Hom.:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.0

DANN

Benign

0.94

DEOGEN2

Benign

0.36

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

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.0020

MetaRNN

Benign

0.016

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

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.085

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

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.76

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

REVEL

Benign

0.072

Sift

Benign

0.49

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

Sift4G

Benign

1.0

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

Polyphen

0.0

B;.;B;.;B;.;.;.;.;.;.;.

Vest4

0.049

MutPred

0.39

Gain of catalytic residue at K1000 (P = 0.0366);.;.;.;Gain of catalytic residue at K1000 (P = 0.0366);.;.;.;.;.;.;.;

MVP

0.31

MPC

0.26

ClinPred

0.035

GERP RS

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.11

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

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