11-74034102-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.769

Publications

8 publications found

Variant links:

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

C2CD3 links:

ENSG00000298570 (HGNC:):

ENSG00000298570 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286577.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD3	NM_001286577.2	MANE Select	c.6058T>C	p.Ser2020Pro	missense	Exon 31 of 33	NP_001273506.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
C2CD3	ENST00000334126.12	TSL:5 MANE Select	c.6058T>C	p.Ser2020Pro	missense	Exon 31 of 33	ENSP00000334379.7
C2CD3	ENST00000680231.1		c.6058T>C	p.Ser2020Pro	missense	Exon 31 of 33	ENSP00000505413.1
C2CD3	ENST00000679906.1		c.6058T>C	p.Ser2020Pro	missense	Exon 31 of 32	ENSP00000505021.1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22244

AN:

151838

Hom.:

4671

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0287

AC XY:

19568

AN XY:

682894

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2052

4105

6157

8210

10262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

832

1664

2496

3328

4160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22319

AN:

151956

Hom.:

4694

Cov.:

AF XY:

0.142

AC XY:

10572

AN XY:

74276

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0186

AC:

1265

AN:

67974

Other (OTH)

AF:

0.105

AC:

221

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

644

1287

1931

2574

3218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0687

Hom.:

2825

Bravo

AF:

0.161

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0132

AC:

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.013

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.10

MetaRNN

Benign

0.00020

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.6

PhyloP100

-0.77

PROVEAN

Benign

0.51

REVEL

Benign

0.0070

Sift

Benign

0.47

Sift4G

Benign

0.25

Vest4

0.027

ClinPred

0.0076

GERP RS

-1.6

Varity_R

0.031

gMVP

0.10

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over