rs12417424

chr11-74040436-G-T

Variant summary

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

The NM_001286577.2(C2CD3):c.5660+1618C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,766 control chromosomes in the GnomAD database, including 2,355 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 0.17 (2355 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2CD3	NM_001286577.2	c.5660+1618C>A		intron_variant		ENST00000334126.12
C2CD3	NM_015531.6	c.5660+1618C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2CD3	ENST00000334126.12	c.5660+1618C>A		intron_variant		5	NM_001286577.2	P2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25590 AN: 151650 Hom.: 2349 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.169 AC: 25620 AN: 151766 Hom.: 2355 Cov.: 32 AF XY: 0.165 AC XY: 12258 AN XY: 74132

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0683

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.177

Alfa AF: 0.182 Hom.: 3269

Bravo AF: 0.176

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.5
Dann	Benign	0.31

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: rs12417424; hg19: chr11-73751481;