chr8-27430997-C-A

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

2
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

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
PTK2BNM_173176.3 linkuse as main transcriptc.791C>A p.Thr264Asn missense_variant 8/31 ENST00000346049.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTK2BENST00000346049.10 linkuse as main transcriptc.791C>A p.Thr264Asn missense_variant 8/311 NM_173176.3 A1Q14289-1

Frequencies

GnomAD3 genomes
AF:
0.00348
AC:
529
AN:
152222
Hom.:
1
Cov.:
33
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.:
5
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.:
20
Cov.:
32
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.:
1
Cov.:
33
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.:
0
Bravo
AF:
0.00408
TwinsUK
AF:
0.00512
AC:
19
ALSPAC
AF:
0.00363
AC:
14
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00442
AC:
38
ExAC
AF:
0.00285
AC:
346
EpiCase
AF:
0.00638
EpiControl
AF:
0.00599

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJun 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.13
T;T;.;.
Eigen
Benign
-0.066
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.86
.;D;D;.
MetaRNN
Benign
0.012
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;N;N
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Benign
0.48
T
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
T
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.

Other links and lift over

dbSNP: rs61738530; hg19: chr8-27288514; COSMIC: COSV57758734; COSMIC: COSV57758734; API