9-136497455-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_017617.5(NOTCH1):c.6284G>A(p.Arg2095His) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,612,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2095C) 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_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000164 AC: 4AN: 243724Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133590
GnomAD4 exome AF: 0.0000377 AC: 55AN: 1460060Hom.: 0 Cov.: 39 AF XY: 0.0000317 AC XY: 23AN XY: 726388
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
The c.6284G>A (p.R2095H) alteration is located in exon 34 (coding exon 34) of the NOTCH1 gene. This alteration results from a G to A substitution at nucleotide position 6284, causing the arginine (R) at amino acid position 2095 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Adams-Oliver syndrome 5 Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at