rs826086

chr11-74052998-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
C2CD3	NM_001286577.2	c.5155+1609C>T		intron_variant		ENST00000334126.12
C2CD3	NM_015531.6	c.5155+1609C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2CD3	ENST00000334126.12	c.5155+1609C>T		intron_variant		5	NM_001286577.2	P2

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

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0189

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00423

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0316 Hom.: 36

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs826086; hg19: chr11-73764043;