ClinVar Miner

Submissions for variant NM_001330360.2(POLA1):c.1393-354A>G

dbSNP: rs869312979
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SNPedia RCV000210684 SCV000266573 pathogenic X-linked reticulate pigmentary disorder criteria provided, single submitter literature only
CeGaT Center for Human Genetics Tuebingen RCV001092577 SCV001249138 pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001092577 SCV002128606 pathogenic not provided 2022-10-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant results in activation of a cryptic donor splice site and introduces a premature termination codon (PMID: 27019227). The resulting mRNA is expected to undergo nonsense-mediated decay. Studies have shown that this variant alters POLA1 gene expression (PMID: 27019227). ClinVar contains an entry for this variant (Variation ID: 224980). This variant has been observed in individuals with X-linked reticulate pigmentary disorder (PMID: 27019227). It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change falls in intron 13 of the POLA1 gene. It does not directly change the encoded amino acid sequence of the POLA1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in POLA1 cause disease.
OMIM RCV000210684 SCV000292424 pathogenic X-linked reticulate pigmentary disorder 2021-03-25 no assertion criteria provided literature only

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