rs144093014

Positions:

• chr15-92955491-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001271.4(CHD2):​c.1788T>C​(p.Tyr596=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,592,496 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (58 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.111

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 15-92955491-T-C is Benign according to our data. Variant chr15-92955491-T-C is described in ClinVar as [Benign]. Clinvar id is 238878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.111 with no splicing effect.
• BS2: High AC in GnomAd4 at 1017 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4	c.1788T>C	p.Tyr596=	synonymous_variant	15/39	ENST00000394196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9	c.1788T>C	p.Tyr596=	synonymous_variant	15/39	5	NM_001271.4	P1

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1017 AN: 152130 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00804

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00564 AC: 1285 AN: 227978 Hom.: 13 AF XY: 0.00546 AC XY: 677 AN XY: 123900

Gnomad AFR exome AF: 0.00128

Gnomad AMR exome AF: 0.00432

Gnomad ASJ exome AF: 0.00262

Gnomad EAS exome AF: 0.0000607

Gnomad SAS exome AF: 0.0000760

Gnomad FIN exome AF: 0.0182

Gnomad NFE exome AF: 0.00657

Gnomad OTH exome AF: 0.00630

GnomAD4 exome AF: 0.00767 AC: 11052 AN: 1440248 Hom.: 58 Cov.: 28 AF XY: 0.00730 AC XY: 5227 AN XY: 716236

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00424

Gnomad4 ASJ exome AF: 0.00191

Gnomad4 EAS exome AF: 0.0000521

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.0180

Gnomad4 NFE exome AF: 0.00855

Gnomad4 OTH exome AF: 0.00658

GnomAD4 genome AF: 0.00668 AC: 1017 AN: 152248 Hom.: 5 Cov.: 33 AF XY: 0.00693 AC XY: 516 AN XY: 74422

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.00804

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00607 Hom.: 2

Bravo AF: 0.00592

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	CHD2: BP4, BP7, BS1, BS2 -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2016

This alteration is classified as 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. -

Developmental and epileptic encephalopathy 94 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.4
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs144093014; hg19: chr15-93498721; COSMIC: COSV104431534; COSMIC: COSV104431534;