chr8-27397646-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173176.3(PTK2B):​c.62G>A​(p.Gly21Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G21A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PTK2B
NM_173176.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23282456).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTK2BNM_173176.3 linkuse as main transcriptc.62G>A p.Gly21Asp missense_variant 2/31 ENST00000346049.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTK2BENST00000346049.10 linkuse as main transcriptc.62G>A p.Gly21Asp missense_variant 2/311 NM_173176.3 A1Q14289-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461888
Hom.:
0
Cov.:
64
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152244
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000274
Hom.:
0

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 GeneticsSep 25, 2023The c.62G>A (p.G21D) alteration is located in exon 7 (coding exon 1) of the PTK2B gene. This alteration results from a G to A substitution at nucleotide position 62, causing the glycine (G) at amino acid position 21 to be replaced by an aspartic acid (D). 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
0.12
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T;T;.;T;.;T;T;.
Eigen
Benign
0.039
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.90
.;D;D;D;D;D;D;.
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
1.8
L;.;.;L;L;.;.;L
MutationTaster
Benign
0.92
D;D;D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0050
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.012
D;D;D;D;D;D;D;D
Polyphen
0.016
B;.;.;B;P;.;.;P
Vest4
0.48
MutPred
0.18
Loss of MoRF binding (P = 0.1153);Loss of MoRF binding (P = 0.1153);Loss of MoRF binding (P = 0.1153);Loss of MoRF binding (P = 0.1153);Loss of MoRF binding (P = 0.1153);Loss of MoRF binding (P = 0.1153);Loss of MoRF binding (P = 0.1153);Loss of MoRF binding (P = 0.1153);
MVP
0.76
MPC
0.46
ClinPred
0.82
D
GERP RS
2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.41
gMVP
0.46

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: rs771540159; hg19: chr8-27255163; API