8-27433522-C-G

Position:

chr8-27433522-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_173176.3(PTK2B):c.1075C>G(p.Gln359Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,614,070 control chromosomes in the GnomAD database, including 10 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

PTK2B
NM_173176.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.891

Variant links:

Genes affected

PTK2B (HGNC:9612): (protein tyrosine kinase 2 beta) This gene encodes a cytoplasmic protein tyrosine kinase which is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. This protein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulator associated with FAK, and the SH2 domain of GRB2. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PTK2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037846565).

BP6

Variant 8-27433522-C-G is Benign according to our data. Variant chr8-27433522-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 775261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 297 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2B	NM_173176.3 linkuse as main transcript	c.1075C>G	p.Gln359Glu	missense_variant	11/31	ENST00000346049.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2B	ENST00000346049.10 linkuse as main transcript	c.1075C>G	p.Gln359Glu	missense_variant	11/31	1	NM_173176.3	A1	Q14289-1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

297

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00251

AC:

631

AN:

251322

Hom.:

AF XY:

0.00263

AC XY:

357

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000897

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00320

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00284

AC:

4157

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

2091

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00304

Gnomad4 OTH exome

AF:

0.00308

GnomAD4 genome

AF:

0.00195

AC:

297

AN:

152380

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.00209

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00246

AC:

299

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00379

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.44

DANN

Benign

0.12

DEOGEN2

Benign

0.079

T;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.76

.;T;T;.

M_CAP

Benign

0.0033

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.7

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.43

N;N;N;N

REVEL

Benign

0.016

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.16

MVP

0.23

MPC

0.32

ClinPred

0.00069

GERP RS

-0.019

Varity_R

0.10

gMVP

0.26

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