Variant 8-27430997-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173176.3(PTK2B):c.791C>A(p.Thr264Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,614,046 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 20 hom. )

Consequence

PTK2B
NM_173176.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.95

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=0.012320578).

BP6

Variant 8-27430997-C-A is Benign according to our data. Variant chr8-27430997-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 788820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 529 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2B	NM_173176.3 linkuse as main transcript	c.791C>A	p.Thr264Asn	missense_variant	8/31	ENST00000346049.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2B	ENST00000346049.10 linkuse as main transcript	c.791C>A	p.Thr264Asn	missense_variant	8/31	1	NM_173176.3	A1	Q14289-1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00488

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00290

AC:

729

AN:

251238

Hom.:

AF XY:

0.00288

AC XY:

391

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000602

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00474

GnomAD4 exome

AF:

0.00428

AC:

6252

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

3036

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.000469

Gnomad4 NFE exome

AF:

0.00500

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152340

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

237

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00488

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00408

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00285

AC:

346

EpiCase

AF:

0.00638

EpiControl

AF:

0.00599

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

T;T;.;.

Eigen

Benign

-0.066

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.86

.;D;D;.

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.67

N;N;N;N

REVEL

Benign

0.091

Sift

Benign

0.57

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.037

B;B;B;B

Vest4

0.47

MVP

0.31

MPC

0.37

ClinPred

0.012

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.37

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