chr8-27422364-C-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_173176.3(PTK2B):c.532C>T(p.Leu178Leu) 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 (★★).
Frequency
Genomes: 𝑓 0.0038 ( 5 hom., cov: 33)
Exomes 𝑓: 0.00062 ( 6 hom. )
Consequence
PTK2B
NM_173176.3 synonymous
NM_173176.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.77
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
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_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.77 with no splicing effect.
BS2
High AC in GnomAd4 at 576 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTK2B | NM_173176.3 | c.532C>T | p.Leu178Leu | synonymous_variant | 5/31 | ENST00000346049.10 | NP_775268.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTK2B | ENST00000346049.10 | c.532C>T | p.Leu178Leu | synonymous_variant | 5/31 | 1 | NM_173176.3 | ENSP00000332816.6 |
Frequencies
GnomAD3 genomes AF: 0.00366 AC: 557AN: 152266Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00133 AC: 330AN: 248618Hom.: 1 AF XY: 0.00126 AC XY: 169AN XY: 134454
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GnomAD4 exome AF: 0.000616 AC: 900AN: 1460826Hom.: 6 Cov.: 30 AF XY: 0.000614 AC XY: 446AN XY: 726716
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GnomAD4 genome AF: 0.00378 AC: 576AN: 152384Hom.: 5 Cov.: 33 AF XY: 0.00380 AC XY: 283AN XY: 74520
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 18, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at