rs61752830
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001271.4(CHD2):c.4978G>A(p.Asp1660Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_001271.4 missense
Scores
Clinical Significance
Conservation
Publications
- complex neurodevelopmental disorderInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- developmental and epileptic encephalopathy 94Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- Lennox-Gastaut syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- myoclonic-astatic epilepsyInheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152102Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000278 AC: 7AN: 251420 AF XY: 0.0000294 show subpopulations
GnomAD4 exome AF: 0.000114 AC: 167AN: 1461888Hom.: 0 Cov.: 35 AF XY: 0.000106 AC XY: 77AN XY: 727246 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000855 AC: 13AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74302 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:1
The CHD2 p.Asp1660Asn variant was not identified in the literature but was identified in dbSNP (ID: rs61752830) and ClinVar (classified as uncertain significance by Invitae for Epileptic encephalopathy, childhood-onset). The variant was identified in control databases in 10 of 282816 chromosomes at a frequency of 0.00003536 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Other in 1 of 7220 chromosomes (freq: 0.000139), European (non-Finnish) in 8 of 129150 chromosomes (freq: 0.000062) and African in 1 of 24962 chromosomes (freq: 0.00004), but was not observed in the Latino, Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. This frequency is greater than expected for rare autosomal dominant CHD2-related neurodevelopmental disorders. The p.Asp1660 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
Developmental and epileptic encephalopathy 94 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at