rs34315566

Positions:

• chr15-93009258-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001271.4(CHD2):​c.4527C>T​(p.Ile1509Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,614,118 control chromosomes in the GnomAD database, including 2,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (239 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2473 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.60

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 15-93009258-C-T is Benign according to our data. Variant chr15-93009258-C-T is described in ClinVar as [Benign]. Clinvar id is 257711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD2	NM_001271.4	c.4527C>T	p.Ile1509Ile	synonymous_variant	35/39	ENST00000394196.9	NP_001262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.4527C>T	p.Ile1509Ile	synonymous_variant	35/39	5	NM_001271.4	ENSP00000377747.4

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6311 AN: 152156 Hom.: 239 Cov.: 33

Gnomad AFR AF: 0.00902

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.0441 AC: 11083 AN: 251356 Hom.: 495 AF XY: 0.0437 AC XY: 5943 AN XY: 135864

Gnomad AFR exome AF: 0.00745

Gnomad AMR exome AF: 0.00960

Gnomad ASJ exome AF: 0.00724

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00902

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.0608

Gnomad OTH exome AF: 0.0396

GnomAD4 exome AF: 0.0509 AC: 74370 AN: 1461844 Hom.: 2473 Cov.: 33 AF XY: 0.0499 AC XY: 36282 AN XY: 727226

Gnomad4 AFR exome AF: 0.00723

Gnomad4 AMR exome AF: 0.00991

Gnomad4 ASJ exome AF: 0.00781

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00974

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.0559

Gnomad4 OTH exome AF: 0.0418

GnomAD4 genome AF: 0.0414 AC: 6309 AN: 152274 Hom.: 239 Cov.: 33 AF XY: 0.0435 AC XY: 3237 AN XY: 74446

Gnomad4 AFR AF: 0.00900

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.0588

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0478 Hom.: 109

Bravo AF: 0.0291

Asia WGS AF: 0.00577 AC: 20 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 09, 2017	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	1.1
DANN	Benign	0.89
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34315566; hg19: chr15-93552488; COSMIC: COSV104431434; COSMIC: COSV104431434;