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GeneBe

8-27422364-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_173176.3(PTK2B):c.532C>T(p.Leu178=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,613,210 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L178L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0038 ( 5 hom., cov: 33)
Exomes 𝑓: 0.00062 ( 6 hom. )

Consequence

PTK2B
NM_173176.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.77
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-27422364-C-T is Benign according to our data. Variant chr8-27422364-C-T is described in ClinVar as [Benign]. Clinvar id is 792104.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.77 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 557 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTK2BNM_173176.3 linkuse as main transcriptc.532C>T p.Leu178= synonymous_variant 5/31 ENST00000346049.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTK2BENST00000346049.10 linkuse as main transcriptc.532C>T p.Leu178= synonymous_variant 5/311 NM_173176.3 A1Q14289-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00366
AC:
557
AN:
152266
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0123
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00133
AC:
330
AN:
248618
Hom.:
1
AF XY:
0.00126
AC XY:
169
AN XY:
134454
show subpopulations
Gnomad AFR exome
AF:
0.0125
Gnomad AMR exome
AF:
0.000553
Gnomad ASJ exome
AF:
0.000500
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00253
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000188
Gnomad OTH exome
AF:
0.000987
GnomAD4 exome
AF:
0.000616
AC:
900
AN:
1460826
Hom.:
6
Cov.:
30
AF XY:
0.000614
AC XY:
446
AN XY:
726716
show subpopulations
Gnomad4 AFR exome
AF:
0.0144
Gnomad4 AMR exome
AF:
0.000584
Gnomad4 ASJ exome
AF:
0.000920
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00233
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000531
Gnomad4 OTH exome
AF:
0.00152
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00378
AC:
576
AN:
152384
Hom.:
5
Cov.:
33
AF XY:
0.00380
AC XY:
283
AN XY:
74520
show subpopulations
Gnomad4 AFR
AF:
0.0127
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00248
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00236
Alfa
AF:
0.00143
Hom.:
0
Bravo
AF:
0.00389
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
12
Dann
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs112665817; hg19: chr8-27279881; API