chr3-50366042-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_006030.4(CACNA2D2):āc.2831A>Cā(p.Asn944Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N944S) has been classified as Uncertain significance.
Frequency
Consequence
NM_006030.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D2 | NM_006030.4 | c.2831A>C | p.Asn944Thr | missense_variant | 32/38 | ENST00000424201.7 | |
LOC101928965 | NR_183064.1 | n.680T>G | non_coding_transcript_exon_variant | 1/2 | |||
LOC127898564 | NR_183066.1 | n.835-255T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.2831A>C | p.Asn944Thr | missense_variant | 32/38 | 1 | NM_006030.4 | P4 | |
ENST00000607121.5 | n.567+102T>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250526Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135566
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461068Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 4AN XY: 726830
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74446
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 08, 2019 | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CACNA2D2-related disease. This variant is present in population databases (rs745846272, ExAC 0.01%). This sequence change replaces asparagine with threonine at codon 944 of the CACNA2D2 protein (p.Asn944Thr). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at