rs12906163

Variant names:

• chr15-93024634-A-C
• rs12906163
• NM_001271.4:c.5416A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-93024634-A-C
• chr15-93024634-A-G
• chr15-93024634-A-T

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.5416A>C​(p.Arg1806Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,613,926 control chromosomes in the GnomAD database, including 108,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7212 hom., cov: 32)
  • Exomes 𝑓: 0.36 (100886 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.978
• Publications: 20 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.65).
• BP6: Variant 15-93024634-A-C is Benign according to our data. Variant chr15-93024634-A-C is described in ClinVar as Benign. ClinVar VariationId is 257713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.978 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 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.5416A>C	p.Arg1806Arg	synonymous	Exon 39 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.5416A>C	p.Arg1806Arg	synonymous	Exon 39 of 39	ENSP00000377747.4	O14647-1
	CHD2	ENST00000625662.3	TSL:5	n.*1587A>C		non_coding_transcript_exon	Exon 35 of 35	ENSP00000486007.2	A0A0D9SEU0
	CHD2	ENST00000627460.1	TSL:5	n.*548A>C		non_coding_transcript_exon	Exon 5 of 5	ENSP00000485982.1	A0A0D9SET4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42904 AN: 152056 Hom.: 7210 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.322

GnomAD2 exomes AF: 0.295 AC: 73504 AN: 249530 AF XY: 0.305

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.183

Gnomad ASJ exome AF: 0.437

Gnomad EAS exome AF: 0.0719

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.361 AC: 527915 AN: 1461752 Hom.: 100886 Cov.: 42 AF XY: 0.360 AC XY: 261745 AN XY: 727180

African (AFR) AF: 0.129 AC: 4312 AN: 33478

American (AMR) AF: 0.192 AC: 8583 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 11345 AN: 26136

East Asian (EAS) AF: 0.0645 AC: 2560 AN: 39700

South Asian (SAS) AF: 0.275 AC: 23749 AN: 86256

European-Finnish (FIN) AF: 0.236 AC: 12622 AN: 53416

Middle Eastern (MID) AF: 0.425 AC: 2452 AN: 5768

European-Non Finnish (NFE) AF: 0.397 AC: 441371 AN: 1111882

Other (OTH) AF: 0.346 AC: 20921 AN: 60394

GnomAD4 genome AF: 0.282 AC: 42922 AN: 152174 Hom.: 7212 Cov.: 32 AF XY: 0.274 AC XY: 20396 AN XY: 74400

African (AFR) AF: 0.136 AC: 5642 AN: 41522

American (AMR) AF: 0.263 AC: 4028 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3468

East Asian (EAS) AF: 0.0728 AC: 378 AN: 5192

South Asian (SAS) AF: 0.252 AC: 1212 AN: 4814

European-Finnish (FIN) AF: 0.227 AC: 2409 AN: 10590

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26526 AN: 67978

Other (OTH) AF: 0.317 AC: 670 AN: 2112

Alfa AF: 0.330 Hom.: 11713

Bravo AF: 0.278

Asia WGS AF: 0.184 AC: 637 AN: 3478

EpiCase AF: 0.418

EpiControl AF: 0.415

ClinVar

ClinVar submissions as Germline

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	-0.65
CADD	Benign	7.9
DANN	Benign	0.68
PhyloP100		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12906163; hg19: chr15-93567864; COSMIC: COSV67710013; COSMIC: COSV67710013;