chr11-74088255-C-T

Variant names:

• chr11-74088255-C-T
• rs826056
• NM_001286577.2:c.3642-2369G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286577.2(C2CD3):​c.3642-2369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,112 control chromosomes in the GnomAD database, including 30,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (30176 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256
• Publications: 4 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

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.3642-2369G>A		intron	N/A	NP_001273506.1	Q4AC94-5
	C2CD3	NM_015531.6		c.3642-2369G>A		intron	N/A	NP_056346.3	Q4AC94-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD3	ENST00000334126.12	TSL:5 MANE Select	c.3642-2369G>A		intron	N/A	ENSP00000334379.7	Q4AC94-5
	C2CD3	ENST00000414160.7	TSL:1	c.3642-2369G>A		intron	N/A	ENSP00000388750.3	H7BZB4
	C2CD3	ENST00000313663.11	TSL:1	c.3642-2369G>A		intron	N/A	ENSP00000323339.7	Q4AC94-1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92298 AN: 151996 Hom.: 30127 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.607 AC: 92405 AN: 152112 Hom.: 30176 Cov.: 32 AF XY: 0.607 AC XY: 45102 AN XY: 74356

African (AFR) AF: 0.874 AC: 36323 AN: 41546

American (AMR) AF: 0.521 AC: 7957 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1698 AN: 3466

East Asian (EAS) AF: 0.459 AC: 2373 AN: 5170

South Asian (SAS) AF: 0.480 AC: 2311 AN: 4814

European-Finnish (FIN) AF: 0.612 AC: 6458 AN: 10550

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33570 AN: 67982

Other (OTH) AF: 0.553 AC: 1170 AN: 2116

Alfa AF: 0.449 Hom.: 1352

Bravo AF: 0.610

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs826056; hg19: chr11-73799300;