ClinVar Miner

Submissions for variant NM_025216.3(WNT10A):c.1087A>C (p.Asn363His) (rs34972707)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000333165 SCV000427601 uncertain significance Schopf-Schulz-Passarge syndrome 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, 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.
Illumina Clinical Services Laboratory,Illumina RCV000387692 SCV000427602 uncertain significance Odonto-onycho-dermal dysplasia 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, 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.
Illumina Clinical Services Laboratory,Illumina RCV000288484 SCV000427603 uncertain significance Tooth agenesis, selective, 4 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, 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.
GeneDx RCV000414053 SCV000491281 likely pathogenic not provided 2018-09-04 criteria provided, single submitter clinical testing The N363H variant in the WNT10A gene has been reported previously in a cohort of individuals with tooth agenesis (Mues et al., 2014); however, the zygosity of the N363H variant or its co-occurrence with other WNT10A variants was not addressed in this publication. The N363H variant has also been reported in trans with another WNT10A pathogenic variant in an individual with tooth agenesis, and was present in the heterozygous state in this individual's unaffected children (Yang et al., 2015). The N363H variant was not observed at any significant frequency in approximately 5300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N363H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R360C, C362R) have been reported in the Human Gene Mutation Database in association with ectodermal dysplasia (Stenson et al., 2014), supporting the functional importance of this region of the protein. The N363H variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV001082463 SCV001020336 benign Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4 2019-12-31 criteria provided, single submitter clinical testing
Yale Center for Mendelian Genomics,Yale University RCV000845114 SCV000987050 pathogenic Reduced number of teeth 2014-09-15 no assertion criteria provided literature only

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