rs201342438
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001194998.2(CEP152):āc.2878T>Cā(p.Trp960Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00365 in 1,591,736 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001194998.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CEP152 | ENST00000380950.7 | c.2878T>C | p.Trp960Arg | missense_variant | Exon 20 of 27 | 1 | NM_001194998.2 | ENSP00000370337.2 | ||
CEP152 | ENST00000399334.7 | c.2878T>C | p.Trp960Arg | missense_variant | Exon 20 of 26 | 1 | ENSP00000382271.3 | |||
CEP152 | ENST00000325747.9 | c.2599T>C | p.Trp867Arg | missense_variant | Exon 19 of 25 | 1 | ENSP00000321000.5 |
Frequencies
GnomAD3 genomes AF: 0.00255 AC: 387AN: 151978Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00253 AC: 591AN: 233654Hom.: 1 AF XY: 0.00251 AC XY: 317AN XY: 126338
GnomAD4 exome AF: 0.00377 AC: 5427AN: 1439640Hom.: 13 Cov.: 32 AF XY: 0.00368 AC XY: 2629AN XY: 713762
GnomAD4 genome AF: 0.00254 AC: 386AN: 152096Hom.: 1 Cov.: 32 AF XY: 0.00231 AC XY: 172AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:2
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Variant previously reported in the heterozygous state in three unrelated individuals with atrioventricular septal defects; however, these individuals did not have features of CEP125-related disorders and did not have a second variant identified in CEP152 (D'Alessandro et al., 2016); 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: 25996639, 31696992, 34402213) -
CEP152: BS2 -
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Microcephaly 9, primary, autosomal recessive Pathogenic:1Uncertain:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Seckel syndrome 5;C3553886:Microcephaly 9, primary, autosomal recessive Uncertain:1
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CEP152-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Seckel syndrome 5 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at