rs826086

Variant names:

• chr11-74052998-G-A
• rs826086
• NM_001286577.2:c.5155+1609C>T

Variant summary

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

The NM_001286577.2(C2CD3):​c.5155+1609C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,272 control chromosomes in the GnomAD database, including 466 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 0.046 (466 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 1 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, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.5155+1609C>T		intron_variant	Intron 26 of 32	ENST00000334126.12	NP_001273506.1
C2CD3	NM_015531.6	c.5155+1609C>T		intron_variant	Intron 26 of 30		NP_056346.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12	c.5155+1609C>T		intron_variant	Intron 26 of 32	5	NM_001286577.2	ENSP00000334379.7

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6964 AN: 152154 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.00423

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0459 AC: 6987 AN: 152272 Hom.: 466 Cov.: 32 AF XY: 0.0446 AC XY: 3321 AN XY: 74468

African (AFR) AF: 0.150 AC: 6209 AN: 41516

American (AMR) AF: 0.0189 AC: 289 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0160 AC: 77 AN: 4826

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10610

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.00423 AC: 288 AN: 68034

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0355 Hom.: 43

Bravo AF: 0.0497

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-0.35
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: rs826086; hg19: chr11-73764043;