chr15-92978374-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy 94

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Lennox-Gastaut syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 257708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD2	NM_001271.4	MANE Select	c.2718A>G	p.Gln906Gln	synonymous	Exon 21 of 39	NP_001262.3	O14647-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD2	ENST00000394196.9	TSL:5 MANE Select	c.2718A>G	p.Gln906Gln	synonymous	Exon 21 of 39	ENSP00000377747.4	O14647-1
	CHD2	ENST00000626874.2	TSL:1	c.2718A>G	p.Gln906Gln	synonymous	Exon 21 of 38	ENSP00000486629.1	O14647-2
	CHD2	ENST00000625463.1	TSL:1	c.258A>G	p.Gln86Gln	synonymous	Exon 3 of 4	ENSP00000486391.1	A0A0D9SF92

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

GnomAD2 exomes AF: 0.844 AC: 210204 AN: 248986 AF XY: 0.850

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 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

African (AFR) AF: 0.565 AC: 18900 AN: 33472

American (AMR) AF: 0.912 AC: 40800 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 23700 AN: 26136

East Asian (EAS) AF: 0.998 AC: 39633 AN: 39696

South Asian (SAS) AF: 0.899 AC: 77554 AN: 86256

European-Finnish (FIN) AF: 0.759 AC: 40562 AN: 53412

Middle Eastern (MID) AF: 0.919 AC: 5303 AN: 5768

European-Non Finnish (NFE) AF: 0.835 AC: 928731 AN: 1111804

Other (OTH) AF: 0.838 AC: 50584 AN: 60390

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

African (AFR) AF: 0.559 AC: 23169 AN: 41428

American (AMR) AF: 0.881 AC: 13454 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5165 AN: 5176

South Asian (SAS) AF: 0.908 AC: 4381 AN: 4824

European-Finnish (FIN) AF: 0.754 AC: 7939 AN: 10536

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56481 AN: 67996

Other (OTH) AF: 0.818 AC: 1725 AN: 2110

Alfa AF: 0.810 Hom.: 44642

Bravo AF: 0.769

Asia WGS AF: 0.931 AC: 3238 AN: 3478

EpiCase AF: 0.851

EpiControl AF: 0.855

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Developmental and epileptic encephalopathy 94 (2)
-	-	2	not provided (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.0
DANN	Benign	0.65
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11074121; hg19: chr15-93521604; COSMIC: COSV108240538; COSMIC: COSV108240538;