chrX-110688709-AC-A

Position:

• chrX-110688709-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001143981.2(CHRDL1):​c.872del​(p.Cys291LeufsTer25) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 20)
• Consequence: CHRDL1 NM_001143981.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.56

Genes affected

CHRDL1 (HGNC:29861): (chordin like 1) This gene encodes an antagonist of bone morphogenetic protein 4. The encoded protein may play a role in topographic retinotectal projection and in the regulation of retinal angiogenesis in response to hypoxia. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-110688709-AC-A is Pathogenic according to our data. Variant chrX-110688709-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 29957.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRDL1	NM_001143981.2	c.872del	p.Cys291LeufsTer25	frameshift_variant	9/12	ENST00000372042.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRDL1	ENST00000372042.6	c.872del	p.Cys291LeufsTer25	frameshift_variant	9/12	2	NM_001143981.2	A1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 20

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Megalocornea Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 10, 2012

- -

Computational scores

Source: dbNSFP v4.3

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: rs398122851; hg19: chrX-109931937;