ClinVar Miner

Submissions for variant NM_000382.3(ALDH3A2):c.471+1del

dbSNP: rs786204741
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169590 SCV000221098 likely pathogenic Sjögren-Larsson syndrome 2015-01-29 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169590 SCV000696650 pathogenic Sjögren-Larsson syndrome 2016-07-08 criteria provided, single submitter clinical testing Variant summary: The ALDH3A2 c.471+1delG variant involves the alteration of a conserved intronic nucleotide located at the invariable GT site at the border of intron 3. One in silico tool predicts a damaging outcome for this variant along with 5/5 splice tools predicting the variant to result in the weakening/elimination of the splice donor site in intron 3. These predictions have been confirmed by studies investigating SLS patients who carried the variant and demonstrated that the variant results in altered mRNA and the absence of the full length protein product. This variant was absent in 121396 control chromosomes, but has been reported in multiple SLS patients in either homozygosity or compound heterozygosity with other splice site or frameshift variants, suggesting pathogenicity. In addition, a clinical diagnostic laboratory classified this variant as Likely Pathogenic via ClinVar (without evidence to independently evaluate). Taken together, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001034892 SCV001198195 pathogenic not provided 2023-12-12 criteria provided, single submitter clinical testing This sequence change affects a splice site in intron 3 of the ALDH3A2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs786204741, gnomAD 0.003%). Disruption of this splice site has been observed in individuals with Sjogren-Larsson syndrome (PMID: 10854114, 21872273). ClinVar contains an entry for this variant (Variation ID: 189163). Studies have shown that disruption of this splice site results in skipping of exons 2-3, but is expected to preserve the integrity of the reading-frame (PMID: 10854114, 21872273). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000169590 SCV001527248 pathogenic Sjögren-Larsson syndrome 2018-09-21 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Fulgent Genetics, Fulgent Genetics RCV000169590 SCV005644796 pathogenic Sjögren-Larsson syndrome 2024-01-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV000169590 SCV002093176 pathogenic Sjögren-Larsson syndrome 2021-02-25 no assertion criteria provided clinical testing

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