rs144093014

Variant names:

• chr15-92955491-T-C
• rs144093014
• NM_001271.4:c.1788T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-92955491-T-C
• chr15-92955491-T-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001271.4(CHD2):​c.1788T>C​(p.Tyr596Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,592,496 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (58 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.111
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 15-92955491-T-C is Benign according to our data. Variant chr15-92955491-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.111 with no splicing effect.
• BS2: High AC in GnomAd4 at 1017 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.1788T>C	p.Tyr596Tyr	synonymous	Exon 15 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.1788T>C	p.Tyr596Tyr	synonymous	Exon 15 of 39	ENSP00000377747.4	O14647-1
	CHD2	ENST00000626874.2	TSL:1	c.1788T>C	p.Tyr596Tyr	synonymous	Exon 15 of 38	ENSP00000486629.1	O14647-2
	CHD2	ENST00000628118.2	TSL:1	n.735T>C		non_coding_transcript_exon	Exon 6 of 23	ENSP00000515059.1	A0A8V8TRB2

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1017 AN: 152130 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00804

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00564 AC: 1285 AN: 227978 AF XY: 0.00546

Gnomad AFR exome AF: 0.00128

Gnomad AMR exome AF: 0.00432

Gnomad ASJ exome AF: 0.00262

Gnomad EAS exome AF: 0.0000607

Gnomad FIN exome AF: 0.0182

Gnomad NFE exome AF: 0.00657

Gnomad OTH exome AF: 0.00630

GnomAD4 exome AF: 0.00767 AC: 11052 AN: 1440248 Hom.: 58 Cov.: 28 AF XY: 0.00730 AC XY: 5227 AN XY: 716236

African (AFR) AF: 0.00131 AC: 42 AN: 32106

American (AMR) AF: 0.00424 AC: 171 AN: 40370

Ashkenazi Jewish (ASJ) AF: 0.00191 AC: 49 AN: 25664

East Asian (EAS) AF: 0.0000521 AC: 2 AN: 38368

South Asian (SAS) AF: 0.000182 AC: 15 AN: 82236

European-Finnish (FIN) AF: 0.0180 AC: 951 AN: 52918

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5722

European-Non Finnish (NFE) AF: 0.00855 AC: 9429 AN: 1103306

Other (OTH) AF: 0.00658 AC: 392 AN: 59558

GnomAD4 genome AF: 0.00668 AC: 1017 AN: 152248 Hom.: 5 Cov.: 33 AF XY: 0.00693 AC XY: 516 AN XY: 74422

African (AFR) AF: 0.00137 AC: 57 AN: 41572

American (AMR) AF: 0.0111 AC: 170 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0194 AC: 205 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00804 AC: 547 AN: 68008

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00607 Hom.: 2

Bravo AF: 0.00592

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Developmental and epileptic encephalopathy 94 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.4
DANN	Benign	0.44
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=87/13	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs144093014; hg19: chr15-93498721; COSMIC: COSV104431534;