rs1685333

Variant names:

• chr11-74017114-A-G
• rs1685333
• NM_001286577.2:c.6922-3589T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-74017114-A-G
• chr11-74017114-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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

ENSG00000298570 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.6922-3589T>C		intron_variant	Intron 32 of 32	ENST00000334126.12	NP_001273506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12	c.6922-3589T>C		intron_variant	Intron 32 of 32	5	NM_001286577.2	ENSP00000334379.7

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

African (AFR) AF: 0.598 AC: 24768 AN: 41448

American (AMR) AF: 0.206 AC: 3147 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1588 AN: 5176

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4820

European-Finnish (FIN) AF: 0.381 AC: 4019 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17047 AN: 67988

Other (OTH) AF: 0.276 AC: 583 AN: 2114

Alfa AF: 0.259 Hom.: 4647

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
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1685333; hg19: chr11-73728159;