Submissions for variant NM_000760.4(CSF3R):c.103A>G (p.Ile35Val)

gnomAD frequency: 0.00003  dbSNP: rs755370892

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768196	SCV000898638	uncertain significance	Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	2018-03-13	criteria provided, single submitter	clinical testing	CSF3R NM_000760.3 exon 4 p.Ile35Val (c.103A>G): This variant has not been reported in the literature but is present in 5/34342 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs755370892). This variant amino acid Valine (Val) is present in >10 species 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000768196	SCV001398462	uncertain significance	Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	2024-11-13	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 35 of the CSF3R protein (p.Ile35Val). This variant is present in population databases (rs755370892, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CSF3R-related conditions. ClinVar contains an entry for this variant (Variation ID: 626094). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CSF3R protein function with a negative predictive value of 80%. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224438	SCV003919858	uncertain significance	Hereditary neutrophilia; Autosomal recessive severe congenital neutropenia due to CSF3R deficiency	2021-12-22	criteria provided, single submitter	clinical testing	CSF3R NM_000760.3 exon 4 p.Ile35Val (c.103A>G): This variant has not been reported in the literature but is present in 5/34342 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs755370892). This variant amino acid Valine (Val) is present in >10 species 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.
Ambry Genetics	RCV004609519	SCV005106198	uncertain significance	Inborn genetic diseases	2024-06-17	criteria provided, single submitter	clinical testing	The c.103A>G (p.I35V) alteration is located in exon 4 (coding exon 2) of the CSF3R gene. This alteration results from a A to G substitution at nucleotide position 103, causing the isoleucine (I) at amino acid position 35 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.