ClinVar Miner

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

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Total submissions: 4
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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.
Invitae RCV001034892 SCV001198195 pathogenic not provided 2019-12-13 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the ALDH3A2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Sjogren-Larsson syndrome (PMID: 21872273). ClinVar contains an entry for this variant (Variation ID: 189163). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 21872273). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ALDH3A2 are known to be pathogenic (PMID: 10577908, 10854114). 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].

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