ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.211_212del (p.Cys71fs) (rs1057516288)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410209 SCV000485417 likely pathogenic Metachromatic leukodystrophy 2015-12-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000410209 SCV001360432 likely pathogenic Metachromatic leukodystrophy 2019-08-29 criteria provided, single submitter clinical testing Variant summary: ARSA c.211_212delTG (p.Cys71HisfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.304delC, p.Leu102fsX6; c.960G>A, p.Trp320X). The variant was absent in 168270 control chromosomes (gnomAD). The variant, c.211_212delTG, has been reported in the literature in one homozygous individual affected with Metachromatic Leukodystrophy (Eng_2003). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submission from other clinical diagnostic laboratories (evaluation after 2014) cited the variant once as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000410209 SCV001589206 pathogenic Metachromatic leukodystrophy 2020-04-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys71Hisfs*4) in the ARSA gene. It is expected to result 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 metachromatic leukodystrophy (PMID: 14517960). This variant is also known as c.205_206delTG (p.Cys69fs) in the literature. ClinVar contains an entry for this variant (Variation ID: 370171). Loss-of-function variants in ARSA are known to be pathogenic (PMID: 8962139, 10477432). For these reasons, this variant has been classified as Pathogenic.

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