ClinVar Miner

Submissions for variant NM_024408.4(NOTCH2):c.6004A>G (p.Asn2002Asp)

gnomAD frequency: 0.00002  dbSNP: rs761367735
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000733330 SCV000861380 uncertain significance not provided 2018-05-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002485928 SCV002776014 uncertain significance Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome 2021-11-21 criteria provided, single submitter clinical testing
Invitae RCV002535322 SCV003475750 uncertain significance Hajdu-Cheney syndrome 2023-06-03 criteria provided, single submitter clinical testing 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 NOTCH2 protein function. ClinVar contains an entry for this variant (Variation ID: 597266). This variant has not been reported in the literature in individuals affected with NOTCH2-related conditions. This variant is present in population databases (rs761367735, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 2002 of the NOTCH2 protein (p.Asn2002Asp). 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.
Ambry Genetics RCV004027058 SCV004990207 uncertain significance Inborn genetic diseases 2024-02-05 criteria provided, single submitter clinical testing The c.6004A>G (p.N2002D) alteration is located in exon 33 (coding exon 33) of the NOTCH2 gene. This alteration results from a A to G substitution at nucleotide position 6004, causing the asparagine (N) at amino acid position 2002 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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