ClinVar Miner

Submissions for variant NM_015443.4(KANSL1):c.122A>G (p.Asn41Ser)

gnomAD frequency: 0.00019  dbSNP: rs142587760
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001705002 SCV000241350 likely benign not provided 2020-03-25 criteria provided, single submitter clinical testing
Invitae RCV000696346 SCV000824903 uncertain significance Koolen-de Vries syndrome 2021-09-21 criteria provided, single submitter clinical testing Due to the possible presence of a polymorphic segmental duplication, the location of the variant could not be unambiguously resolved. Variants with ambiguous mapping are still reported relative to the KANSL1 transcript. This sequence change replaces asparagine with serine at codon 41 of the KANSL1 or 17q21.31 segmental duplication protein (p.Asn41Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 205765). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Until the location of this sequence change can be resolved, the clinical significance of this variant remains uncertain. It has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000696346 SCV002495813 uncertain significance Koolen-de Vries syndrome 2022-02-03 criteria provided, single submitter clinical testing KANSL1 NM_001193466.1 exon 2 p.Asn41Ser (c.122A>G): This variant has not been reported in the literature but is present in 0.03% (16/41472) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-46172022-T-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:205765). This variant amino acid Serine (Ser) is present in several species including mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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