9-136496339-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_017617.5(NOTCH1):c.7400C>T(p.Ser2467Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000148 in 1,593,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S2467S) has been classified as Likely benign.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.7400C>T | p.Ser2467Leu | missense_variant | 34/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.6677C>T | p.Ser2226Leu | missense_variant | 31/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.7400C>T | p.Ser2467Leu | missense_variant | 34/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000125 AC: 27AN: 215786Hom.: 0 AF XY: 0.000144 AC XY: 17AN XY: 117734
GnomAD4 exome AF: 0.000152 AC: 219AN: 1440838Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 106AN XY: 714664
GnomAD4 genome AF: 0.000105 AC: 16AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74352
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 14, 2020 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Blueprint Genetics | Jan 28, 2014 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 16, 2023 | Has not been previously reported in association with TAAD to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30341550, 24728327) - |
Adams-Oliver syndrome 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at