2-216482762-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014140.4(SMARCAL1):c.2650G>A(p.Asp884Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014140.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251292Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135806
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727234
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74270
ClinVar
Submissions by phenotype
Schimke immuno-osseous dysplasia Uncertain:3
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 884 of the SMARCAL1 protein (p.Asp884Asn). This variant is present in population databases (rs763712548, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1004836). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. -
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Inborn genetic diseases Uncertain:1
The c.2650G>A (p.D884N) alteration is located in exon 18 (coding exon 16) of the SMARCAL1 gene. This alteration results from a G to A substitution at nucleotide position 2650, causing the aspartic acid (D) at amino acid position 884 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at