chr15-93014765-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_001271.4(CHD2):c.4762C>T(p.Arg1588Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000844 in 1,614,100 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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. R1588Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001271.4 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 |
---|---|---|---|---|---|---|---|
CHD2 | NM_001271.4 | c.4762C>T | p.Arg1588Trp | missense_variant | 37/39 | ENST00000394196.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD2 | ENST00000394196.9 | c.4762C>T | p.Arg1588Trp | missense_variant | 37/39 | 5 | NM_001271.4 | P1 | |
CHD2 | ENST00000626874.2 | c.4762C>T | p.Arg1588Trp | missense_variant | 37/38 | 1 | |||
CHD2 | ENST00000625662.3 | c.*933C>T | 3_prime_UTR_variant, NMD_transcript_variant | 33/35 | 5 | ||||
CHD2 | ENST00000627460.1 | c.48+39C>T | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000480 AC: 73AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000310 AC: 78AN: 251468Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135910
GnomAD4 exome AF: 0.000882 AC: 1289AN: 1461888Hom.: 2 Cov.: 31 AF XY: 0.000854 AC XY: 621AN XY: 727248
GnomAD4 genome AF: 0.000480 AC: 73AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74418
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy 94 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 18, 2019 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | CHD2: BS2 - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
CHD2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 13, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at