rs75423398
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_024408.4(NOTCH2):c.3779G>A(p.Arg1260His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,614,178 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1260C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024408.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH2 | NM_024408.4 | c.3779G>A | p.Arg1260His | missense_variant | 23/34 | ENST00000256646.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH2 | ENST00000256646.7 | c.3779G>A | p.Arg1260His | missense_variant | 23/34 | 1 | NM_024408.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000894 AC: 136AN: 152174Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.00144 AC: 361AN: 251456Hom.: 6 AF XY: 0.00135 AC XY: 183AN XY: 135910
GnomAD4 exome AF: 0.00165 AC: 2411AN: 1461886Hom.: 99 Cov.: 32 AF XY: 0.00164 AC XY: 1195AN XY: 727246
GnomAD4 genome AF: 0.000886 AC: 135AN: 152292Hom.: 4 Cov.: 32 AF XY: 0.000953 AC XY: 71AN XY: 74472
ClinVar
Submissions by phenotype
Hajdu-Cheney syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | NOTCH2: PP2, BP4, BS1, BS2 - |
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