rs12417424

Variant names:

• chr11-74040436-G-T
• rs12417424
• NM_001286577.2:c.5660+1618C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.88).
• 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 rank	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.5660+1618C>A		intron_variant	Intron 29 of 32	ENST00000334126.12	NP_001273506.1
C2CD3	NM_015531.6	c.5660+1618C>A		intron_variant	Intron 29 of 30		NP_056346.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12	c.5660+1618C>A		intron_variant	Intron 29 of 32	5	NM_001286577.2	ENSP00000334379.7

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

African (AFR) AF: 0.126 AC: 5210 AN: 41386

American (AMR) AF: 0.252 AC: 3838 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 501 AN: 3462

East Asian (EAS) AF: 0.0683 AC: 354 AN: 5182

South Asian (SAS) AF: 0.101 AC: 484 AN: 4806

European-Finnish (FIN) AF: 0.163 AC: 1705 AN: 10442

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12902 AN: 67920

Other (OTH) AF: 0.177 AC: 372 AN: 2106

Alfa AF: 0.182 Hom.: 4250

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
PhyloP100		0.37
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: rs12417424; hg19: chr11-73751481;