rs1685333

chr11-74017114-A-Gchr11-74017114-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286577.2(C2CD3):c.6922-3589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,076 control chromosomes in the GnomAD database, including 11,324 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 0.35 (11324 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2CD3	NM_001286577.2	c.6922-3589T>C		intron_variant		ENST00000334126.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2CD3	ENST00000334126.12	c.6922-3589T>C		intron_variant		5	NM_001286577.2	P2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53395 AN: 151958 Hom.: 11296 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.352 AC: 53467 AN: 152076 Hom.: 11324 Cov.: 32 AF XY: 0.352 AC XY: 26185 AN XY: 74342

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.276

Alfa AF: 0.254 Hom.: 3765

Bravo AF: 0.345

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	4.0
Dann	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1685333; hg19: chr11-73728159;