NM_001271.4:c.693-20C>T

Variant names:

• chr15-92941802-C-T
• rs141271290
• NM_001271.4:c.693-20C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001271.4(CHD2):​c.693-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,609,170 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0080 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (388 hom.)
• Consequence: CHD2 NM_001271.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.128

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 15-92941802-C-T is Benign according to our data. Variant chr15-92941802-C-T is described in ClinVar as [Benign]. Clinvar id is 257715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-92941802-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4	c.693-20C>T		intron_variant	Intron 7 of 38	ENST00000394196.9	NP_001262.3
CHD2	NM_001042572.3	c.693-20C>T		intron_variant	Intron 7 of 12		NP_001036037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.693-20C>T		intron_variant	Intron 7 of 38	5	NM_001271.4	ENSP00000377747.4

Frequencies

GnomAD3 genomes AF: 0.00803 AC: 1222 AN: 152098 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0174 AC: 4333 AN: 248624 Hom.: 281 AF XY: 0.0131 AC XY: 1763 AN XY: 134510

Gnomad AFR exome AF: 0.00112

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00778

Gnomad SAS exome AF: 0.00120

Gnomad FIN exome AF: 0.000603

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.00434 AC: 6330 AN: 1456954 Hom.: 388 Cov.: 29 AF XY: 0.00381 AC XY: 2762 AN XY: 724950

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.120

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0125

Gnomad4 SAS exome AF: 0.00156

Gnomad4 FIN exome AF: 0.000844

Gnomad4 NFE exome AF: 0.0000856

Gnomad4 OTH exome AF: 0.00434

GnomAD4 genome AF: 0.00803 AC: 1223 AN: 152216 Hom.: 56 Cov.: 32 AF XY: 0.00894 AC XY: 665 AN XY: 74420

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000944

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00400 Hom.: 12

Bravo AF: 0.0145

Asia WGS AF: 0.00664 AC: 23 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 30% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 28. Only high quality variants are reported. -

Jan 20, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Developmental and epileptic encephalopathy 94 Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.63
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141271290; hg19: chr15-93485032; COSMIC: COSV104400294; COSMIC: COSV104400294;