ClinVar Miner

Submissions for variant NM_018136.5(ASPM):c.3978G>A (p.Trp1326Ter)

dbSNP: rs137852995
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV000005249 SCV002058172 pathogenic Microcephaly 5, primary, autosomal recessive 2022-01-03 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported to be associated with ASPM related disorder (ClinVar ID: VCV000004961, PMID:15355437).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). The variant has been reported to be in trans as homozygous in at least one similarly affected unrelated individual (PMID: 15355437,PM3_P). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae RCV002512801 SCV003524015 pathogenic not provided 2022-05-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1326*) in the ASPM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASPM are known to be pathogenic (PMID: 19028728, 23611254). This variant is present in population databases (rs137852995, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with primary microcephaly (PMID: 15355437, 31853109). ClinVar contains an entry for this variant (Variation ID: 4961). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000005249 SCV004178687 pathogenic Microcephaly 5, primary, autosomal recessive 2023-04-11 criteria provided, single submitter clinical testing
OMIM RCV000005249 SCV000025427 pathogenic Microcephaly 5, primary, autosomal recessive 2004-10-01 no assertion criteria provided literature only
GeneReviews RCV000005249 SCV000041354 not provided Microcephaly 5, primary, autosomal recessive no assertion provided literature only

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