rs201620755
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_017617.5(NOTCH1):c.2434G>C(p.Gly812Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G812A) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.2434G>C | p.Gly812Arg | missense_variant | 15/34 | ENST00000651671.1 | |
LOC124902310 | XR_007061865.1 | n.507+3075C>G | intron_variant, non_coding_transcript_variant | ||||
NOTCH1 | XM_011518717.3 | c.1711G>C | p.Gly571Arg | missense_variant | 12/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.2434G>C | p.Gly812Arg | missense_variant | 15/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248020Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135098
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460484Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 726528
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jan 03, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at