rs826071

Variant names:

• chr11-74034102-A-G
• rs826071
• NM_001286577.2:c.6058T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001286577.2(C2CD3):​c.6058T>C​(p.Ser2020Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 1,535,882 control chromosomes in the GnomAD database, including 9,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (4694 hom., cov: 32)
  • Exomes 𝑓: 0.030 (4482 hom.)
• Consequence: C2CD3 NM_001286577.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.769
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0325184E-4).
• BP6: Variant 11-74034102-A-G is Benign according to our data. Variant chr11-74034102-A-G is described in ClinVar as Benign. ClinVar VariationId is 1274269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.6058T>C	p.Ser2020Pro	missense_variant	Exon 31 of 33	ENST00000334126.12	NP_001273506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12	c.6058T>C	p.Ser2020Pro	missense_variant	Exon 31 of 33	5	NM_001286577.2	ENSP00000334379.7

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22244 AN: 151838 Hom.: 4671 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0437 AC: 5995 AN: 137184 AF XY: 0.0381

Gnomad AFR exome AF: 0.487

Gnomad AMR exome AF: 0.0271

Gnomad ASJ exome AF: 0.0292

Gnomad EAS exome AF: 0.00542

Gnomad FIN exome AF: 0.0216

Gnomad NFE exome AF: 0.0184

Gnomad OTH exome AF: 0.0385

GnomAD4 exome AF: 0.0301 AC: 41690 AN: 1383926 Hom.: 4482 Cov.: 33 AF XY: 0.0287 AC XY: 19568 AN XY: 682894

African (AFR) AF: 0.500 AC: 15783 AN: 31594

American (AMR) AF: 0.0309 AC: 1103 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 740 AN: 25182

East Asian (EAS) AF: 0.0190 AC: 679 AN: 35734

South Asian (SAS) AF: 0.0252 AC: 1997 AN: 79236

European-Finnish (FIN) AF: 0.0213 AC: 724 AN: 33958

Middle Eastern (MID) AF: 0.0612 AC: 349 AN: 5698

European-Non Finnish (NFE) AF: 0.0161 AC: 17386 AN: 1078894

Other (OTH) AF: 0.0506 AC: 2929 AN: 57928

GnomAD4 genome AF: 0.147 AC: 22319 AN: 151956 Hom.: 4694 Cov.: 32 AF XY: 0.142 AC XY: 10572 AN XY: 74276

African (AFR) AF: 0.470 AC: 19452 AN: 41352

American (AMR) AF: 0.0542 AC: 828 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 125 AN: 3466

East Asian (EAS) AF: 0.00812 AC: 42 AN: 5174

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4810

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10590

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0186 AC: 1265 AN: 67974

Other (OTH) AF: 0.105 AC: 221 AN: 2102

Alfa AF: 0.0687 Hom.: 2825

Bravo AF: 0.161

TwinsUK AF: 0.0140 AC: 52

ALSPAC AF: 0.0132 AC: 51

ExAC AF: 0.0450 AC: 963

Asia WGS AF: 0.0530 AC: 188 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.91
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.00020	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.77
PROVEAN	Benign	0.51	N
REVEL	Benign	0.0070
Sift	Benign	0.47	T
Sift4G	Benign	0.25	T
Vest4		0.027
ClinPred		0.0076	T
GERP RS		-1.6
Varity_R		0.031
gMVP		0.10
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs826071; hg19: chr11-73745147; COSMIC: COSV58093392; COSMIC: COSV58093392;