ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.8245A>G (p.Ile2749Val)

gnomAD frequency: 0.00013  dbSNP: rs186436335
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000473308 SCV000552975 likely benign Spastic paraplegia 2024-03-13 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000594324 SCV000702728 uncertain significance not provided 2016-11-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765121 SCV000896343 uncertain significance Charlevoix-Saguenay spastic ataxia 2018-10-31 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000594324 SCV001713619 uncertain significance not provided 2019-07-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848817 SCV002105093 uncertain significance Hereditary spastic paraplegia 2021-02-12 criteria provided, single submitter clinical testing
Athena Diagnostics RCV004999477 SCV005621876 likely benign not specified 2023-11-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004999477 SCV006071512 uncertain significance not specified 2025-03-24 criteria provided, single submitter clinical testing Variant summary: SACS c.8245A>G (p.Ile2749Val) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 1613960 control chromosomes in the gnomAD database, including 1 homozygotes (gnomAD v4). This frequency is not significantly higher than estimated for a pathogenic variant in SACS causing Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay (0.00028 vs 0.0079), allowing no conclusion about variant significance. c.8245A>G has been reported in the literature in individuals affected with Ataxia (Ngo_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31692161). ClinVar contains an entry for this variant (Variation ID: 411694). Based on the evidence outlined above, the variant was classified as uncertain significance.

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