ClinVar Miner

Submissions for variant NM_005219.5(DIAPH1):c.2224C>G (p.Pro742Ala)

gnomAD frequency: 0.00036  dbSNP: rs199749212
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000652774 SCV000774645 uncertain significance Autosomal dominant nonsyndromic hearing loss 1; Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 742 of the DIAPH1 protein (p.Pro742Ala). This variant is present in population databases (rs199749212, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with DIAPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 542364). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000652774 SCV000897208 uncertain significance Autosomal dominant nonsyndromic hearing loss 1; Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825744 SCV000967203 likely benign not specified 2018-12-23 criteria provided, single submitter clinical testing The p.Pro742Ala variant in DIAPH1 is classified as likely benign because it has been identified in 0.05% (63/128264) of European chromosomes including 1 homozyg ote by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1 .
Illumina Laboratory Services, Illumina RCV001155495 SCV001316923 uncertain significance Autosomal dominant nonsyndromic hearing loss 1 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 RCV001592824 SCV001826417 uncertain significance not provided 2019-11-12 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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