rs114626664
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003672.4(CDC14A):c.608-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,607,152 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 5 hom. )
Consequence
CDC14A
NM_003672.4 splice_polypyrimidine_tract, intron
NM_003672.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001859
2
Clinical Significance
Conservation
PhyloP100: -0.217
Genes affected
CDC14A (HGNC:1718): (cell division cycle 14A) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. It is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, suggesting a role in cell cycle control. This protein has been shown to interact with, and dephosphorylate tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in several transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 1-100462641-G-A is Benign according to our data. Variant chr1-100462641-G-A is described in ClinVar as [Benign]. Clinvar id is 506036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00417 (635/152240) while in subpopulation AFR AF= 0.0142 (591/41550). AF 95% confidence interval is 0.0133. There are 3 homozygotes in gnomad4. There are 317 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC14A | NM_003672.4 | c.608-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000336454.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC14A | ENST00000336454.5 | c.608-10G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003672.4 | A1 | |||
ENST00000432210.1 | n.350C>T | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00415 AC: 632AN: 152122Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000993 AC: 249AN: 250820Hom.: 3 AF XY: 0.000767 AC XY: 104AN XY: 135590
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GnomAD4 exome AF: 0.000400 AC: 582AN: 1454912Hom.: 5 Cov.: 28 AF XY: 0.000351 AC XY: 254AN XY: 724304
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GnomAD4 genome ? AF: 0.00417 AC: 635AN: 152240Hom.: 3 Cov.: 32 AF XY: 0.00426 AC XY: 317AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 14, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2017 | c.608-10G>A in intron 8 of CDC14A: This variant is not expected to have clinical significance because it has been identified in 1.32% (135/10232) of African chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs114626664). - |
CDC14A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 14, 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). - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at