rs587783436

chr8-60822092-CAG-C

Variant summary

Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1 PP5_Very_Strong

The NM_017780.4(CHD7):c.2905_2906del(p.Arg969GlyfsTer25) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD7 NM_017780.4 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 10.0

Genes affected

CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Pathogenic. Variant got 16 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 8-60822092-CAG-C is Pathogenic according to our data. Variant chr8-60822092-CAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 158287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD7	NM_017780.4	c.2905_2906del	p.Arg969GlyfsTer25	frameshift_variant	11/38	ENST00000423902.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD7	ENST00000423902.7	c.2905_2906del	p.Arg969GlyfsTer25	frameshift_variant	11/38	5	NM_017780.4	P1
CHD7	ENST00000524602.5	c.1717-40136_1717-40135del		intron_variant		1
CHD7	ENST00000525508.1	c.2905_2906del	p.Arg969GlyfsTer25	frameshift_variant	10/12	5
CHD7	ENST00000695853.1	c.2905_2906del	p.Arg969GlyfsTer25	frameshift_variant, NMD_transcript_variant	11/37

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CHARGE syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Sep 21, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs587783436; hg19: chr8-61734651;