rs1726764

Variant names:

• chr11-74020619-C-T
• rs1726764
• NM_001286577.2:c.6922-7094G>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.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
• Publications: 7 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=-0.91).
• 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 rank	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.6922-7094G>A		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.6922-7094G>A		intron_variant	Intron 32 of 32	5	NM_001286577.2	ENSP00000334379.7

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

African (AFR) AF: 0.742 AC: 30784 AN: 41512

American (AMR) AF: 0.504 AC: 7700 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1566 AN: 3466

East Asian (EAS) AF: 0.446 AC: 2310 AN: 5180

South Asian (SAS) AF: 0.448 AC: 2160 AN: 4824

European-Finnish (FIN) AF: 0.612 AC: 6467 AN: 10572

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34465 AN: 67942

Other (OTH) AF: 0.500 AC: 1054 AN: 2110

Alfa AF: 0.523 Hom.: 15679

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
PhyloP100		-0.95
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: rs1726764; hg19: chr11-73731664;