Variant chr11-74034102-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/16 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
C2CD3	NM_001286577.2 linkuse as main transcript	c.6058T>C	p.Ser2020Pro	missense_variant	31/33	ENST00000334126.12	NP_001273506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12 linkuse as main transcript	c.6058T>C	p.Ser2020Pro	missense_variant	31/33	5	NM_001286577.2	ENSP00000334379	P2	Q4AC94-5

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

GnomAD3 exomes

AF:

0.0437

AC:

5995

AN:

137184

Hom.:

835

AF XY:

0.0381

AC XY:

2838

AN XY:

74442

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 SAS exome

AF:

0.0253

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

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.0309

Gnomad4 ASJ exome

AF:

0.0294

Gnomad4 EAS exome

AF:

0.0190

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.0213

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0506

GnomAD4 genome

AF:

0.147

AC:

22319

AN:

151956

Hom.:

4694

Cov.:

AF XY:

0.142

AC XY:

10572

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.0542

Gnomad4 ASJ

AF:

0.0361

Gnomad4 EAS

AF:

0.00812

Gnomad4 SAS

AF:

0.0212

Gnomad4 FIN

AF:

0.0246

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0719

Hom.:

430

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

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

MutationTaster

Benign

1.0

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over