chr14-91272686-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001080414.4(CCDC88C):c.6026C>T(p.Pro2009Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,611,648 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P2009P) has been classified as Likely benign.
Frequency
Consequence
NM_001080414.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CCDC88C | ENST00000389857.11 | c.6026C>T | p.Pro2009Leu | missense_variant | Exon 30 of 30 | 5 | NM_001080414.4 | ENSP00000374507.6 | ||
CCDC88C | ENST00000556726 | c.*1860C>T | 3_prime_UTR_variant | Exon 7 of 7 | 5 | ENSP00000452406.1 |
Frequencies
GnomAD3 genomes AF: 0.000716 AC: 109AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000602 AC: 146AN: 242694Hom.: 0 AF XY: 0.000632 AC XY: 84AN XY: 132940
GnomAD4 exome AF: 0.00113 AC: 1643AN: 1459312Hom.: 3 Cov.: 29 AF XY: 0.00109 AC XY: 792AN XY: 726006
GnomAD4 genome AF: 0.000722 AC: 110AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000671 AC XY: 50AN XY: 74488
ClinVar
Submissions by phenotype
not provided Uncertain:5
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 11, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2009 of the CCDC88C protein (p.Pro2009Leu). This variant is present in population databases (rs201940261, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CCDC88C-related conditions. ClinVar contains an entry for this variant (Variation ID: 444336). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2023 | Reported in the heterozygous state in a patient with cerebellar ataxia (Ghorbani et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35401678) - |
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Spinocerebellar ataxia type 40 Uncertain:1
Uncertain significance, no assertion criteria provided | research | O&I group, Department of Genetics, University Medical Center of Groningen | Jul 22, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2022 | The c.6026C>T (p.P2009L) alteration is located in exon 30 (coding exon 30) of the CCDC88C gene. This alteration results from a C to T substitution at nucleotide position 6026, causing the proline (P) at amino acid position 2009 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hydrocephalus, nonsyndromic, autosomal recessive 1;C4518336:Spinocerebellar ataxia type 40 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at