Submissions for variant NM_005359.6(SMAD4):c.424+6T>C

gnomAD frequency: 0.00001  dbSNP: rs771456293

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000582033	SCV000691415	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-26	criteria provided, single submitter	clinical testing	This variant causes a T to C nucleotide substitution at the +6 position of intron 3 of the SMAD4 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/251232 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx	RCV000608629	SCV000719493	likely benign	not specified	2017-05-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000806604	SCV000946611	likely benign	Juvenile polyposis syndrome	2023-11-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002529283	SCV003745305	uncertain significance	Inborn genetic diseases	2022-03-15	criteria provided, single submitter	clinical testing	The c.424+6T>C intronic alteration consists of a T to C substitution 6 nucleotides after exon 3 (coding exon 2) of the SMAD4 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.