rs56003471
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001382273.1(TNK2):c.351C>T(p.Leu117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,614,064 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 25 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 32 hom. )
Consequence
TNK2
NM_001382273.1 synonymous
NM_001382273.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.788
Genes affected
TNK2 (HGNC:19297): (tyrosine kinase non receptor 2) This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 3-195884917-G-A is Benign according to our data. Variant chr3-195884917-G-A is described in ClinVar as [Benign]. Clinvar id is 259880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.788 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1684/152338) while in subpopulation AFR AF= 0.0388 (1612/41568). AF 95% confidence interval is 0.0372. There are 25 homozygotes in gnomad4. There are 825 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1684 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNK2 | NM_001382273.1 | c.351C>T | p.Leu117= | synonymous_variant | 4/16 | ENST00000672887.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNK2 | ENST00000672887.2 | c.351C>T | p.Leu117= | synonymous_variant | 4/16 | NM_001382273.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0111 AC: 1684AN: 152220Hom.: 25 Cov.: 33
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GnomAD3 exomes AF: 0.00263 AC: 659AN: 250726Hom.: 9 AF XY: 0.00196 AC XY: 266AN XY: 135670
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GnomAD4 exome AF: 0.00109 AC: 1589AN: 1461726Hom.: 32 Cov.: 31 AF XY: 0.000931 AC XY: 677AN XY: 727168
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GnomAD4 genome ? AF: 0.0111 AC: 1684AN: 152338Hom.: 25 Cov.: 33 AF XY: 0.0111 AC XY: 825AN XY: 74494
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at