ClinVar Miner

Submissions for variant NM_000430.4(PAFAH1B1):c.162del (p.Lys54fs) (rs113994198)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000020302 SCV000804441 pathogenic Lissencephaly 1 2017-08-28 criteria provided, single submitter provider interpretation This 5 year old male with global developmental delays, seizure disorder, and subcortical band heterotopia was found to carry a variant in the PAFAH1B1 gene, also known as LIS1. The patient is mosaic for this variant, at an unknown level. A paternal sample is unavailable, so inheritance of the variant is unknown, but it is assumed to be de novo. The c.162delA variant has been reported multiple times previously in association with lissencephaly (Sakamoto et al., 1998; de Wit et al., 2011; Dobyns and Das, 2014). Other researchers have identified patients who had subcortical band heterotopia that had somatic mosaicism for variants in the PAFAH1B1 gene (PMIDs: 10441340, 11502906, 14581661); their phenotypes were noted to be less severe than individuals not mosaic for the variants.
GeneDx RCV000255298 SCV000322035 pathogenic not provided 2017-02-21 criteria provided, single submitter clinical testing The c.162delA pathogenic variant in the PAFAH1B1 gene has been reported multiple times previously in association with lissencephaly (Sakamoto et al., 1998; de Wit et al., 2011; Dobyns and Das, 2014). The deletion causes a frameshift starting with codon Lysine 54, changes this amino acid to an Asparagine residue and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Lys54AsnfsX15. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Of note, the NHLBI Exome Sequencing Project reports c.162delA was observed in 37/4,040 (0.9%) of alleles from individuals of African American background and in 63/7,990 (0.8%) alleles from individuals of European American background; however, this data is noted to be of low quality and likely represents an artifact.
GeneReviews RCV000020302 SCV000040670 pathologic Lissencephaly 1 2009-03-03 no assertion criteria provided curation Converted during submission to Pathogenic.
Genetic Services Laboratory, University of Chicago RCV000020302 SCV000194363 pathogenic Lissencephaly 1 2013-02-08 criteria provided, single submitter clinical testing

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