X-110694266-GCG-TTA

Variant names:

• chrX-110694266-GCG-TTA
• NM_001143981.2:c.673_675delCGCinsTAA
• CHRDL1 p.Arg225*

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_001143981.2(CHRDL1):​c.673_675delCGCinsTAA​(p.Arg225*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CHRDL1 NM_001143981.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	NM_001143981.2	MANE Select	c.673_675delCGCinsTAA	p.Arg225*	stop_gained	N/A	NP_001137453.1	Q9BU40-4
	CHRDL1	NM_001367204.1		c.673_675delCGCinsTAA	p.Arg225*	stop_gained	N/A	NP_001354133.1	Q9BU40-4
	CHRDL1	NM_001143982.2		c.670_672delCGCinsTAA	p.Arg224*	stop_gained	N/A	NP_001137454.1	Q9BU40-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	ENST00000372042.6	TSL:2 MANE Select	c.673_675delCGCinsTAA	p.Arg225*	stop_gained	N/A	ENSP00000361112.1	Q9BU40-4
	CHRDL1	ENST00000444321.2	TSL:1	c.670_672delCGCinsTAA	p.Arg224*	stop_gained	N/A	ENSP00000399739.2	Q9BU40-5
	CHRDL1	ENST00000372045.5	TSL:1	c.652_654delCGCinsTAA	p.Arg218*	stop_gained	N/A	ENSP00000361115.1	A0A452Q6Z9

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-109937494;