chr11-74702843-TTC-CTG

Variant names:

• chr11-74702843-TTC-CTG
• NM_001278473.3:c.1069_1071delGAAinsCAG
• CHRDL2 p.Glu357Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001278473.3(CHRDL2):​c.1069_1071delGAAinsCAG​(p.Glu357Gln) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E357K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRDL2 NM_001278473.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11
• Publications: 0 publications found

Genes affected

CHRDL2 (HGNC:24168): (chordin like 2) This gene encodes a member of the chordin family of proteins. Chordin family members are secreted proteins that share a cysteine-rich pro-collagen repeat domain and associate with members of the transforming growth factor beta superfamily. In vitro assays demonstrate a direct interaction between the encoded protein and human activin A. This gene is expressed in many tissues including osteoblasts, where it is differentially expressed during differentiation. In addition, its expression is upregulated in human osteoarthritic joint cartilage, suggesting a role in adult cartilage regeneration. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278473.3. 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
	CHRDL2	NM_001278473.3	MANE Select	c.1069_1071delGAAinsCAG	p.Glu357Gln	missense	N/A	NP_001265402.1	Q6WN34-1
	CHRDL2	NM_015424.6		c.1069_1071delGAAinsCAG	p.Glu357Gln	missense	N/A	NP_056239.3
	CHRDL2	NM_001304390.2		c.1009_1011delGAAinsCAG	p.Glu337Gln	missense	N/A	NP_001291319.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRDL2	ENST00000376332.8	TSL:1 MANE Select	c.1069_1071delGAAinsCAG	p.Glu357Gln	missense	N/A	ENSP00000365510.3	Q6WN34-1
	CHRDL2	ENST00000263671.9	TSL:1	c.1069_1071delGAAinsCAG	p.Glu357Gln	missense	N/A	ENSP00000263671.5	Q6WN34-2
	CHRDL2	ENST00000528789.1	TSL:1	c.874_876delGAAinsCAG	p.Glu292Gln	missense	N/A	ENSP00000431380.1	Q6WN33

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1

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: chr11-74413888;