chrX-110688773-TGA-T

Variant names:

• chrX-110688773-TGA-T
• rs863225435
• NM_001143981.2:c.807_808delTC

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_001143981.2(CHRDL1):​c.807_808delTC​(p.His270TrpfsTer22) variant causes a frameshift change involving the alteration of a conserved nucleotide. 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:2
• Conservation: PhyloP100: 7.75
• Publications: 2 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 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant X-110688773-TGA-T is Pathogenic according to our data. Variant chrX-110688773-TGA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 218164.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL1	NM_001143981.2	MANE Select	c.807_808delTC	p.His270TrpfsTer22	frameshift	Exon 9 of 12	NP_001137453.1	Q9BU40-4
	CHRDL1	NM_001367204.1		c.807_808delTC	p.His270TrpfsTer22	frameshift	Exon 9 of 12	NP_001354133.1	Q9BU40-4
	CHRDL1	NM_001143982.2		c.804_805delTC	p.His269TrpfsTer22	frameshift	Exon 9 of 12	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.807_808delTC	p.His270TrpfsTer22	frameshift	Exon 9 of 12	ENSP00000361112.1	Q9BU40-4
	CHRDL1	ENST00000444321.2	TSL:1	c.804_805delTC	p.His269TrpfsTer22	frameshift	Exon 9 of 12	ENSP00000399739.2	Q9BU40-5
	CHRDL1	ENST00000372045.5	TSL:1	c.786_787delTC	p.His263TrpfsTer22	frameshift	Exon 9 of 12	ENSP00000361115.1	A0A452Q6Z9

Frequencies

GnomAD3 genomes Cov.: 20

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

GnomAD4 genome Cov.: 20

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
2	-	-	Megalocornea (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7
Mutation Taster		=3/197	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

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

Other links and lift over

dbSNP: rs863225435;

hg19: chrX-109932001;