rs371742334
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PP2PP3_ModerateBP6_Moderate
The NM_017617.5(NOTCH1):c.6475C>T(p.Arg2159Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000807 in 1,611,036 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2159H) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 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 |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.6475C>T | p.Arg2159Cys | missense_variant | 34/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.5752C>T | p.Arg1918Cys | missense_variant | 31/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.6475C>T | p.Arg2159Cys | missense_variant | 34/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245404Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134156
GnomAD4 exome AF: 0.00000823 AC: 12AN: 1458848Hom.: 0 Cov.: 39 AF XY: 0.00000827 AC XY: 6AN XY: 725828
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
Adams-Oliver syndrome 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at