15-92992967-C-T

Variant names:

• chr15-92992967-C-T
• rs2272457
• NM_001271.4:c.3564C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001271.4(CHD2):​c.3564C>T​(p.Tyr1188Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,568 control chromosomes in the GnomAD database, including 56,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4435 hom., cov: 33)
  • Exomes 𝑓: 0.26 (51711 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0580
• Publications: 19 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 15-92992967-C-T is Benign according to our data. Variant chr15-92992967-C-T is described in ClinVar as Benign. ClinVar VariationId is 257709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.058 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 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.3564C>T	p.Tyr1188Tyr	synonymous	Exon 28 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.3564C>T	p.Tyr1188Tyr	synonymous	Exon 28 of 39	ENSP00000377747.4	O14647-1
	CHD2	ENST00000626874.2	TSL:1	c.3564C>T	p.Tyr1188Tyr	synonymous	Exon 28 of 38	ENSP00000486629.1	O14647-2
	CHD2	ENST00000628118.2	TSL:1	n.*833C>T		non_coding_transcript_exon	Exon 19 of 23	ENSP00000515059.1	A0A8V8TRB2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35359 AN: 152008 Hom.: 4433 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.264

GnomAD2 exomes AF: 0.225 AC: 56331 AN: 250532 AF XY: 0.230

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.261 AC: 381880 AN: 1461442 Hom.: 51711 Cov.: 34 AF XY: 0.260 AC XY: 189057 AN XY: 727000

African (AFR) AF: 0.193 AC: 6453 AN: 33470

American (AMR) AF: 0.170 AC: 7598 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7376 AN: 26130

East Asian (EAS) AF: 0.151 AC: 6003 AN: 39696

South Asian (SAS) AF: 0.210 AC: 18079 AN: 86242

European-Finnish (FIN) AF: 0.155 AC: 8283 AN: 53384

Middle Eastern (MID) AF: 0.357 AC: 1997 AN: 5598

European-Non Finnish (NFE) AF: 0.279 AC: 310745 AN: 1111838

Other (OTH) AF: 0.254 AC: 15346 AN: 60368

GnomAD4 genome AF: 0.233 AC: 35380 AN: 152126 Hom.: 4435 Cov.: 33 AF XY: 0.229 AC XY: 17040 AN XY: 74382

African (AFR) AF: 0.188 AC: 7811 AN: 41504

American (AMR) AF: 0.229 AC: 3494 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3466

East Asian (EAS) AF: 0.135 AC: 702 AN: 5182

South Asian (SAS) AF: 0.211 AC: 1018 AN: 4814

European-Finnish (FIN) AF: 0.139 AC: 1473 AN: 10590

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18868 AN: 67982

Other (OTH) AF: 0.264 AC: 556 AN: 2110

Alfa AF: 0.267 Hom.: 25319

Bravo AF: 0.238

Asia WGS AF: 0.186 AC: 646 AN: 3478

EpiCase AF: 0.305

EpiControl AF: 0.305

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	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	-0.39
CADD	Benign	6.7
DANN	Benign	0.89
PhyloP100		0.058
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2272457; hg19: chr15-93536197; COSMIC: COSV67710004; COSMIC: COSV67710004;