15-92984389-C-T

Variant names:

• chr15-92984389-C-T
• rs150268140
• NM_001271.4:c.3126C>T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001271.4(CHD2):​c.3126C>T​(p.Asp1042Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,608,960 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (19 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0780

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 15-92984389-C-T is Benign according to our data. Variant chr15-92984389-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 238879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-92984389-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.078 with no splicing effect.
• BS2: High AC in GnomAd4 at 535 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4	c.3126C>T	p.Asp1042Asp	synonymous_variant	Exon 25 of 39	ENST00000394196.9	NP_001262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.3126C>T	p.Asp1042Asp	synonymous_variant	Exon 25 of 39	5	NM_001271.4	ENSP00000377747.4
CHD2	ENST00000637789.1	n.-70C>T		upstream_gene_variant		5		ENSP00000489767.1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 151860 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00438

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00477

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00411 AC: 1017 AN: 247564 Hom.: 3 AF XY: 0.00439 AC XY: 588 AN XY: 133852

Gnomad AFR exome AF: 0.000809

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.0000999

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00294

Gnomad FIN exome AF: 0.0100

Gnomad NFE exome AF: 0.00534

Gnomad OTH exome AF: 0.00401

GnomAD4 exome AF: 0.00407 AC: 5926 AN: 1456984 Hom.: 19 Cov.: 31 AF XY: 0.00420 AC XY: 3047 AN XY: 724774

Gnomad4 AFR exome AF: 0.000600

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00336

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00429

Gnomad4 OTH exome AF: 0.00364

GnomAD4 genome AF: 0.00352 AC: 535 AN: 151976 Hom.: 1 Cov.: 32 AF XY: 0.00372 AC XY: 276 AN XY: 74282

Gnomad4 AFR AF: 0.000700

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00438

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.00477

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00238 Hom.: 1

Bravo AF: 0.00292

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00504

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Feb 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 02, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Mar 02, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHD2: BP4, BP7, BS1, BS2 -

Developmental and epileptic encephalopathy 94 Benign:2

May 23, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Jul 15, 2016

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.3
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs150268140; hg19: chr15-93527619; COSMIC: COSV104431536; COSMIC: COSV104431536;