rs747022065
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_017617.5(NOTCH1):c.6949G>A(p.Gly2317Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. G2317A) has been classified as Uncertain significance.
Frequency
Consequence
NM_017617.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH1 | NM_017617.5 | c.6949G>A | p.Gly2317Ser | missense_variant | 34/34 | ENST00000651671.1 | |
NOTCH1 | XM_011518717.3 | c.6226G>A | p.Gly2076Ser | missense_variant | 31/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH1 | ENST00000651671.1 | c.6949G>A | p.Gly2317Ser | missense_variant | 34/34 | NM_017617.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247264Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 134940
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460540Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 726576
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74368
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 27, 2022 | The c.6949G>A (p.G2317S) 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 6949, causing the glycine (G) at amino acid position 2317 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Adams-Oliver syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at