rs777219891
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_017617.5(NOTCH1):c.6343G>C(p.Glu2115Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2115K) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.6343G>C | p.Glu2115Gln | missense_variant | 34/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.5620G>C | p.Glu1874Gln | missense_variant | 31/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.6343G>C | p.Glu2115Gln | missense_variant | 34/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000824 AC: 2AN: 242706Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133058
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458176Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0AN XY: 725536
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | The p.E2115Q variant (also known as c.6343G>C), located in coding exon 34 of the NOTCH1 gene, results from a G to C substitution at nucleotide position 6343. The glutamic acid at codon 2115 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at