15-92978374-A-G

Variant names:

• chr15-92978374-A-G
• rs11074121
• NM_001271.4:c.2718A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001271.4(CHD2):​c.2718A>G​(p.Gln906Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,613,670 control chromosomes in the GnomAD database, including 562,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46139 hom., cov: 31)
  • Exomes 𝑓: 0.84 (516624 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.64

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 15-92978374-A-G is Benign according to our data. Variant chr15-92978374-A-G is described in ClinVar as [Benign]. Clinvar id is 257708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-92978374-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4	c.2718A>G	p.Gln906Gln	synonymous_variant	Exon 21 of 39	ENST00000394196.9	NP_001262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.2718A>G	p.Gln906Gln	synonymous_variant	Exon 21 of 39	5	NM_001271.4	ENSP00000377747.4

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116496 AN: 151902 Hom.: 46101 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.816

GnomAD3 exomes AF: 0.844 AC: 210204 AN: 248986 Hom.: 89953 AF XY: 0.850 AC XY: 114551 AN XY: 134774

Gnomad AFR exome AF: 0.559

Gnomad AMR exome AF: 0.918

Gnomad ASJ exome AF: 0.906

Gnomad EAS exome AF: 0.998

Gnomad SAS exome AF: 0.900

Gnomad FIN exome AF: 0.765

Gnomad NFE exome AF: 0.831

Gnomad OTH exome AF: 0.858

GnomAD4 exome AF: 0.839 AC: 1225767 AN: 1461650 Hom.: 516624 Cov.: 52 AF XY: 0.841 AC XY: 611422 AN XY: 727140

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.912

Gnomad4 ASJ exome AF: 0.907

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.899

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.835

Gnomad4 OTH exome AF: 0.838

GnomAD4 genome AF: 0.767 AC: 116584 AN: 152020 Hom.: 46139 Cov.: 31 AF XY: 0.772 AC XY: 57365 AN XY: 74294

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.818

Alfa AF: 0.811 Hom.: 33550

Bravo AF: 0.769

Asia WGS AF: 0.931 AC: 3238 AN: 3478

EpiCase AF: 0.851

EpiControl AF: 0.855

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 90. Only high quality variants are reported. -

Jan 05, 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. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy 94 Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Jan 08, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.0
DANN	Benign	0.65
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: rs11074121; hg19: chr15-93521604;