ClinVar Miner

Submissions for variant NM_004525.3(LRP2):c.10415A>G (p.Asn3472Ser)

gnomAD frequency: 0.00004  dbSNP: rs755241846
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001987729 SCV002224951 uncertain significance not provided 2022-05-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 3472 of the LRP2 protein (p.Asn3472Ser). This variant is present in population databases (rs755241846, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LRP2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LRP2 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV001987729 SCV002770407 uncertain significance not provided 2023-03-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Fulgent Genetics, Fulgent Genetics RCV002497846 SCV002777844 uncertain significance Donnai-Barrow syndrome 2022-04-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004043777 SCV004898562 uncertain significance Inborn genetic diseases 2023-09-23 criteria provided, single submitter clinical testing The c.10415A>G (p.N3472S) alteration is located in exon 54 (coding exon 54) of the LRP2 gene. This alteration results from a A to G substitution at nucleotide position 10415, causing the asparagine (N) at amino acid position 3472 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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