chr11-74028287-CT-GG

Variant names:

• chr11-74028287-CT-GG
• NM_001286577.2:c.6920_6921delAGinsCC
• C2CD3 p.Gln2307Pro

Variant summary

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

The NM_001286577.2(C2CD3):​c.6920_6921delAGinsCC​(p.Gln2307Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C2CD3 NM_001286577.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• Publications: 0 publications found

Genes affected

C2CD3 (HGNC:24564): (C2 domain containing 3 centriole elongation regulator) This gene encodes a protein that functions as a regulator of centriole elongation. Studies of the orthologous mouse protein show that it promotes centriolar distal appendage assembly and is also required for the recruitment of other ciliogenic proteins, including intraflagellar transport proteins. Mutations in this gene cause orofaciodigital syndrome XIV (OFD14), a ciliopathy resulting in malformations of the oral cavity, face and digits. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]

C2CD3 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome type 14

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

ENSG00000298570 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286577.2. 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
	C2CD3	NM_001286577.2	MANE Select	c.6920_6921delAGinsCC	p.Gln2307Pro	missense splice_region	N/A	NP_001273506.1	Q4AC94-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD3	ENST00000334126.12	TSL:5 MANE Select	c.6920_6921delAGinsCC	p.Gln2307Pro	missense splice_region	N/A	ENSP00000334379.7	Q4AC94-5
	C2CD3	ENST00000680231.1		c.6920_6921delAGinsCC	p.Gln2307Pro	missense splice_region	N/A	ENSP00000505413.1	A0A7P0Z475
	C2CD3	ENST00000681143.1		c.6515_6516delAGinsCC	p.Gln2172Pro	missense splice_region	N/A	ENSP00000505970.1	A0A7P0Z4H1

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		2.9

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: chr11-73739332;