rs4777755

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001271.4(CHD2):​c.2049A>C​(p.Glu683Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E683E) has been classified as Benign.

Frequency

Genomes: not found (cov: 29)

Consequence

CHD2
NM_001271.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.420
Variant links:
Genes affected
CHD2 (HGNC:1917): (chromodomain helicase DNA binding protein 2) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the CHD2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 57 curated pathogenic missense variants (we use a threshold of 10). The gene has 104 curated benign missense variants. Gene score misZ: 5.2052 (above the threshold of 3.09). Trascript score misZ: 6.0204 (above the threshold of 3.09). GenCC associations: The gene is linked to developmental and epileptic encephalopathy 94, complex neurodevelopmental disorder, myoclonic-astatic epilepsy, Lennox-Gastaut syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.2022672).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHD2NM_001271.4 linkc.2049A>C p.Glu683Asp missense_variant Exon 17 of 39 ENST00000394196.9 NP_001262.3 O14647-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHD2ENST00000394196.9 linkc.2049A>C p.Glu683Asp missense_variant Exon 17 of 39 5 NM_001271.4 ENSP00000377747.4 O14647-1

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Benign
0.41
.;T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.44
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
0.48
.;N
REVEL
Benign
0.21
Sift
Benign
0.45
.;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
B;B
Vest4
0.15
MutPred
0.42
Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
0.69
MPC
1.2
ClinPred
0.087
T
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.053
gMVP
0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4777755; hg19: chr15-93510603; API