chr1-119922639-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_024408.4(NOTCH2):c.4999G>A(p.Val1667Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,614,022 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. V1667F) has been classified as Likely benign.
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.4999G>A | p.Val1667Ile | missense_variant | 27/34 | ENST00000256646.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH2 | ENST00000256646.7 | c.4999G>A | p.Val1667Ile | missense_variant | 27/34 | 1 | NM_024408.4 | P1 | |
NOTCH2 | ENST00000493703.1 | n.409G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00211 AC: 321AN: 152174Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00185 AC: 466AN: 251354Hom.: 1 AF XY: 0.00193 AC XY: 262AN XY: 135850
GnomAD4 exome AF: 0.00303 AC: 4433AN: 1461730Hom.: 7 Cov.: 32 AF XY: 0.00301 AC XY: 2189AN XY: 727172
GnomAD4 genome ? AF: 0.00210 AC: 320AN: 152292Hom.: 1 Cov.: 32 AF XY: 0.00193 AC XY: 144AN XY: 74472
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | NOTCH2: PP2, BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2020 | This variant is associated with the following publications: (PMID: 30304577, 28776642) - |
not specified Benign:2Other:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 13, 2017 | - - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Hajdu-Cheney syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Hajdu-Cheney syndrome;C1857761:Alagille syndrome due to a NOTCH2 point mutation Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 08, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at