Variant 15-93020014-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001271.4(CHD2):c.4909C>G(p.Arg1637Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,456,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CHD2
NM_001271.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

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]

CHD2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CHD2. . Gene score misZ 5.2052 (greater than the threshold 3.09). Trascript score misZ 6.0204 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy 94, complex neurodevelopmental disorder, myoclonic-astatic epilepsy, Lennox-Gastaut syndrome.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD2	NM_001271.4 linkuse as main transcript	c.4909C>G	p.Arg1637Gly	missense_variant, splice_region_variant	38/39	ENST00000394196.9	NP_001262.3	O14647-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9 linkuse as main transcript	c.4909C>G	p.Arg1637Gly	missense_variant, splice_region_variant	38/39	5	NM_001271.4	ENSP00000377747.4		O14647-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249928

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456646

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723406

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy 94

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 10, 2023

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬† is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CHD2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1637 of the CHD2 protein (p.Arg1637Gly). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.8

.;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.0080

.;D

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.57

MutPred

0.26

Loss of MoRF binding (P = 0.0054);Loss of MoRF binding (P = 0.0054);

MVP

0.98

MPC

0.32

ClinPred

0.74

GERP RS

4.6

Varity_R

0.20

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over