ClinVar Miner

Submissions for variant NM_001194998.2(CEP152):c.794A>C (p.Gln265Pro) (rs267606717)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000000072 SCV000192745 likely pathogenic Primary autosomal recessive microcephaly 9 2014-07-24 criteria provided, single submitter clinical testing
GeneDx RCV000413650 SCV000491286 likely pathogenic not provided 2016-02-10 criteria provided, single submitter clinical testing The Q265P variant has been reported previously, in both the homozygous and compound heterozygous state, in individuals with primary microcephaly (Guernsey et al., 2010). The Q265P variant was not observed with any significant frequency in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The Q265P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Fulgent Genetics,Fulgent Genetics RCV000763360 SCV000894050 pathogenic Seckel syndrome 5; Primary autosomal recessive microcephaly 9 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778440 SCV000914686 likely pathogenic CEP152-Related Disorders 2017-09-01 criteria provided, single submitter clinical testing The CEP152 c.794A>C (p.Gln265Pro) missense variant has been reported in one study in which it was found in three individuals with microcephaly, with head circumferences between five and seven standard deviations below the mean, including in two individuals in a homozygous state and in one individual in a compound heterozygous state with a null variant on the second allele (Guernsey et al. 2010). The p.Gln265Pro variant was found in a heterozygous state in each of the unaffected parents of the affected individuals. The p.Gln265Pro variant was absent from 496 control chromosomes including 310 local Maritime control chromosomes and 186 European control chromosomes from the Centre d'Etude du Polymorphisme Humain (CEPH) (Guernsey et al. 2010). The variant is reported at a frequency of 0.000027 in the European (non-Finnish) population of the Genome Aggregation Database. Transfection of the variant protein into human U2OS osteosarcoma-derived cells did not affect localization, with the variant protein being found in the centrosomes similarly to wild type. However, the Gln265 residue is highly conserved among vertebrates and is predicted to fall in a coiled-coiled region predicted to be disrupted by substitution of a proline residue (Guernsey et al. 2010). Based on the evidence, the c.794A>C (p.Gln265Pro) variant is classified as likely pathogenic for CEP152-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000000072 SCV000020215 pathogenic Primary autosomal recessive microcephaly 9 2010-07-09 no assertion criteria provided literature only

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