15-92900836-A-G

Position:

• chr15-92900836-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001271.4(CHD2):​c.-72+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 407,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: CHD2 NM_001271.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 15-92900836-A-G is Benign according to our data. Variant chr15-92900836-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 384922.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-92900836-A-G is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD2	NM_001271.4	c.-72+12A>G		intron_variant		ENST00000394196.9	NP_001262.3
CHD2	NM_001042572.3	c.-72+12A>G		intron_variant			NP_001036037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.-72+12A>G		intron_variant		5	NM_001271.4	ENSP00000377747	P1

Frequencies

GnomAD3 genomes AF: 0.000396 AC: 60 AN: 151598 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000395

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000950

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.000483

GnomAD4 exome AF: 0.000629 AC: 161 AN: 255990 Hom.: 0 Cov.: 0 AF XY: 0.000764 AC XY: 100 AN XY: 130854

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000796

Gnomad4 ASJ exome AF: 0.000320

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000439

Gnomad4 NFE exome AF: 0.000850

Gnomad4 OTH exome AF: 0.000177

GnomAD4 genome AF: 0.000395 AC: 60 AN: 151716 Hom.: 0 Cov.: 31 AF XY: 0.000337 AC XY: 25 AN XY: 74108

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000395

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000950

Gnomad4 NFE AF: 0.000721

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000318 Hom.: 0

Bravo AF: 0.000461

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs545891757; hg19: chr15-93444066;