X-110762798-GTC-G

Variant names:

• chrX-110762798-GTC-G
• rs398122852
• NM_001143981.2:c.102_103delGA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001143981.2(CHRDL1):​c.102_103delGA​(p.Glu34AspfsTer14) variant causes a frameshift change. 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: 22)
• Consequence: CHRDL1 NM_001143981.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.15
• Publications: 1 publications found

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]

CHRDL1 Gene-Disease associations (from GenCC):

• isolated congenital megalocornea

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Pathogenic. The variant received 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-110762798-GTC-G is Pathogenic according to our data. Variant chrX-110762798-GTC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 29960.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143981.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	NM_001143981.2	MANE Select	c.102_103delGA	p.Glu34AspfsTer14	frameshift	Exon 3 of 12	NP_001137453.1
	CHRDL1	NM_001367204.1		c.102_103delGA	p.Glu34AspfsTer14	frameshift	Exon 3 of 12	NP_001354133.1
	CHRDL1	NM_001143982.2		c.102_103delGA	p.Glu34AspfsTer14	frameshift	Exon 3 of 12	NP_001137454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	ENST00000372042.6	TSL:2 MANE Select	c.102_103delGA	p.Glu34AspfsTer14	frameshift	Exon 3 of 12	ENSP00000361112.1
	CHRDL1	ENST00000444321.2	TSL:1	c.102_103delGA	p.Glu34AspfsTer14	frameshift	Exon 3 of 12	ENSP00000399739.2
	CHRDL1	ENST00000372045.5	TSL:1	c.84_85delGA	p.Glu28AspfsTer14	frameshift	Exon 3 of 12	ENSP00000361115.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Megalocornea Pathogenic:1

Feb 10, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1
Mutation Taster		=0/200	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs398122852; hg19: chrX-110006026;