ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.2580A>G (p.Gln860=) (rs41283958)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000712969 SCV000843529 uncertain significance not provided 2018-01-26 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765125 SCV000896349 uncertain significance Charlevoix-Saguenay spastic ataxia 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001087176 SCV001001807 likely benign Spastic paraplegia 2020-12-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000765125 SCV001269524 uncertain significance Charlevoix-Saguenay spastic ataxia 2018-03-16 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Baylor Genetics RCV000765125 SCV001519940 uncertain significance Charlevoix-Saguenay spastic ataxia 2019-12-20 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Nilou-Genome Lab RCV000765125 SCV001712298 uncertain significance Charlevoix-Saguenay spastic ataxia 2021-05-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV000765125 SCV001464175 likely benign Charlevoix-Saguenay spastic ataxia 2020-01-08 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000712969 SCV001552625 uncertain significance not provided no assertion criteria provided clinical testing The SACS p.Gln860Gln variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs41283958), ClinVar (classified as a VUS by Athena Diagnostics and Fulgent Genetics) and LOVD 3.0 (classified as likely benign). The variant was identified in control databases in 85 of 281874 chromosomes (1 homozygous) at a frequency of 0.000302 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 7 of 7184 chromosomes (freq: 0.000974), European (non-Finnish) in 61 of 128904 chromosomes (freq: 0.000473), South Asian in 8 of 30396 chromosomes (freq: 0.000263), Latino in 5 of 35336 chromosomes (freq: 0.000142), African in 3 of 24676 chromosomes (freq: 0.000122) and European (Finnish) in 1 of 25090 chromosomes (freq: 0.00004), while the variant was not observed in the Ashkenazi Jewish, and East Asian populations. The p.Gln860Gln variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (MaxEntScan, NNSPLICE, GeneSplicer) do not predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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