rs763586960
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PP2PP3_ModerateBP6_Moderate
The NM_001271.4(CHD2):c.1321A>T(p.Ile441Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 1 hom. )
Consequence
CHD2
NM_001271.4 missense
NM_001271.4 missense
Scores
9
5
1
Clinical Significance
Conservation
PhyloP100: 5.90
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CHD2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.882
BP6
?
Variant 15-92946160-A-T is Benign according to our data. Variant chr15-92946160-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 541366.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD2 | NM_001271.4 | c.1321A>T | p.Ile441Phe | missense_variant | 12/39 | ENST00000394196.9 | |
CHD2 | NM_001042572.3 | c.1321A>T | p.Ile441Phe | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD2 | ENST00000394196.9 | c.1321A>T | p.Ile441Phe | missense_variant | 12/39 | 5 | NM_001271.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251272Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135788
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461532Hom.: 1 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727086
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GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152354Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74506
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy 94 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 19, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;.;H;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;.;.;D
Vest4
MutPred
Loss of stability (P = 0.0883);Loss of stability (P = 0.0883);.;Loss of stability (P = 0.0883);.;
MVP
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at