chr17-39462342-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_016507.4(CDK12):c.271C>T(p.Leu91=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,614,214 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 61 hom. )
Consequence
CDK12
NM_016507.4 synonymous
NM_016507.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0680
Genes affected
CDK12 (HGNC:24224): (cyclin dependent kinase 12) Enables RNA polymerase II CTD heptapeptide repeat kinase activity and cyclin binding activity. Involved in phosphorylation of RNA polymerase II C-terminal domain; protein autophosphorylation; and regulation of MAP kinase activity. Located in nuclear speck. Part of cyclin K-CDK12 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 17-39462342-C-T is Benign according to our data. Variant chr17-39462342-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1678978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.068 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00104 (158/152322) while in subpopulation SAS AF= 0.0302 (146/4830). AF 95% confidence interval is 0.0262. There are 1 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 160 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK12 | NM_016507.4 | c.271C>T | p.Leu91= | synonymous_variant | 1/14 | ENST00000447079.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK12 | ENST00000447079.6 | c.271C>T | p.Leu91= | synonymous_variant | 1/14 | 1 | NM_016507.4 | P4 | |
CDK12 | ENST00000430627.6 | c.271C>T | p.Leu91= | synonymous_variant | 1/14 | 1 | A1 | ||
CDK12 | ENST00000584632.5 | c.271C>T | p.Leu91= | synonymous_variant | 1/13 | 5 | |||
CDK12 | ENST00000559663.2 | c.271C>T | p.Leu91= | synonymous_variant, NMD_transcript_variant | 1/21 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00105 AC: 160AN: 152204Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00376 AC: 946AN: 251444Hom.: 20 AF XY: 0.00519 AC XY: 706AN XY: 135912
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GnomAD4 exome AF: 0.00182 AC: 2659AN: 1461892Hom.: 61 Cov.: 32 AF XY: 0.00267 AC XY: 1944AN XY: 727246
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CDK12-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary breast ovarian cancer syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | National Health Laboratory Service, Universitas Academic Hospital and University of the Free State | Apr 19, 2022 | - - |
Computational scores
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Name
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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