8-140664946-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001352702.2(PTK2):ā€‹c.3049C>Gā€‹(p.Pro1017Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

PTK2
NM_001352702.2 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.58
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTK2NM_001352702.2 linkc.3049C>G p.Pro1017Ala missense_variant 35/36 ENST00000696786.1 NP_001339631.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTK2ENST00000696786.1 linkc.3049C>G p.Pro1017Ala missense_variant 35/36 NM_001352702.2 ENSP00000512868.1 A0A8Q3WLM4

Frequencies

GnomAD3 genomes
AF:
0.0000593
AC:
9
AN:
151726
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000218
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250956
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135602
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461654
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000593
AC:
9
AN:
151726
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74076
show subpopulations
Gnomad4 AFR
AF:
0.000218
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000907
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsOct 05, 2021The c.2983C>G (p.P995A) alteration is located in exon 31 (coding exon 30) of the PTK2 gene. This alteration results from a C to G substitution at nucleotide position 2983, causing the proline (P) at amino acid position 995 to be replaced by an alanine (A). 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
0.099
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T;.;T;T;T;.;.;.;T;T;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
.;D;D;.;D;D;D;D;D;D;D
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.72
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.8
L;.;.;.;L;.;.;.;.;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-3.9
D;.;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
0.34
Sift
Benign
0.048
D;.;T;T;D;T;T;D;T;D;T
Sift4G
Benign
0.070
T;T;T;T;T;T;T;T;T;T;T
Polyphen
1.0
D;.;P;.;D;.;.;.;.;.;.
Vest4
0.74
MVP
0.66
MPC
1.1
ClinPred
0.98
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.51
gMVP
0.36

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.

Other links and lift over

dbSNP: rs139442064; hg19: chr8-141675045; API