ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3030C>T (p.His1010=) (rs367642503)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231286 SCV000288340 likely benign Neuroblastoma 3 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000231286 SCV001304212 likely benign Neuroblastoma 3 2018-01-13 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Integrated Genetics/Laboratory Corporation of America RCV001193222 SCV001361939 benign not specified 2019-05-14 criteria provided, single submitter clinical testing Variant summary: ALK c.3030C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.8e-05 in 251458 control chromosomes (gnomAD). The observed variant frequency is approximately 114 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALK causing Neuroblastoma, Susceptibility Type 3 phenotype (4.2e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3030C>T in individuals affected with Neuroblastoma, Susceptibility Type 3 and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submission from clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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