rs1726764

chr11-74020619-C-T

Variant summary

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

The NM_001286577.2(C2CD3):c.6922-7094G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,080 control chromosomes in the GnomAD database, including 25,752 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 0.57 (25752 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2CD3	NM_001286577.2	c.6922-7094G>A		intron_variant		ENST00000334126.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2CD3	ENST00000334126.12	c.6922-7094G>A		intron_variant		5	NM_001286577.2	P2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86864 AN: 151962 Hom.: 25724 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.572 AC: 86942 AN: 152080 Hom.: 25752 Cov.: 32 AF XY: 0.571 AC XY: 42469 AN XY: 74348

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.500

Alfa AF: 0.523 Hom.: 11677

Bravo AF: 0.568

Asia WGS AF: 0.450 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.29
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1726764; hg19: chr11-73731664;