15-92984389-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 Benign/Likely_benign. ClinVar VariationId is 238879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.078 with no splicing effect.
• BS2: High AC in GnomAd4 at 535 Unknown,AD gene.

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.3126C>T	p.Asp1042Asp	synonymous	Exon 25 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.3126C>T	p.Asp1042Asp	synonymous	Exon 25 of 39	ENSP00000377747.4	O14647-1
	CHD2	ENST00000626874.2	TSL:1	c.3126C>T	p.Asp1042Asp	synonymous	Exon 25 of 38	ENSP00000486629.1	O14647-2
	CHD2	ENST00000628118.2	TSL:1	n.*395C>T		non_coding_transcript_exon	Exon 16 of 23	ENSP00000515059.1	A0A8V8TRB2

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

GnomAD2 exomes AF: 0.00411 AC: 1017 AN: 247564 AF XY: 0.00439

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 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

African (AFR) AF: 0.000600 AC: 20 AN: 33328

American (AMR) AF: 0.00215 AC: 95 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00336 AC: 287 AN: 85328

European-Finnish (FIN) AF: 0.0101 AC: 539 AN: 53306

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5756

European-Non Finnish (NFE) AF: 0.00429 AC: 4754 AN: 1109368

Other (OTH) AF: 0.00364 AC: 219 AN: 60162

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

African (AFR) AF: 0.000700 AC: 29 AN: 41458

American (AMR) AF: 0.00327 AC: 50 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00438 AC: 21 AN: 4792

European-Finnish (FIN) AF: 0.0102 AC: 108 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00477 AC: 324 AN: 67952

Other (OTH) AF: 0.00143 AC: 3 AN: 2102

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

ClinVar submissions

Significance: Benign/Likely 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	-0.32
CADD	Benign	8.3
DANN	Benign	0.57
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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