chr11-74013467-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001286577.2(C2CD3):c.6980A>G(p.Asn2327Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,428,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

C2CD3
NM_001286577.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.265

Publications

0 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, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029470623).

BP6

Variant 11-74013467-T-C is Benign according to our data. Variant chr11-74013467-T-C is described in ClinVar as Benign. ClinVar VariationId is 1651482.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00104 (158/152038) while in subpopulation AFR AF = 0.00357 (148/41456). AF 95% confidence interval is 0.0031. There are 0 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD3	NM_001286577.2	MANE Select	c.6980A>G	p.Asn2327Ser	missense	Exon 33 of 33	NP_001273506.1	Q4AC94-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2CD3	ENST00000334126.12	TSL:5 MANE Select	c.6980A>G	p.Asn2327Ser	missense	Exon 33 of 33	ENSP00000334379.7	Q4AC94-5
C2CD3	ENST00000681143.1		c.6575A>G	p.Asn2192Ser	missense	Exon 30 of 30	ENSP00000505970.1	A0A7P0Z4H1
C2CD3	ENST00000923534.1		c.6485A>G	p.Asn2162Ser	missense	Exon 32 of 32	ENSP00000593593.1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000962

GnomAD2 exomes

AF:

0.000149

AC:

AN:

60260

AF XY:

0.000117

show subpopulations

Gnomad AFR exome

AF:

0.00382

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000107

AC:

136

AN:

1276608

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

627476

show subpopulations

African (AFR)

AF:

0.00435

AC:

116

AN:

26662

American (AMR)

AF:

0.00

AC:

AN:

19322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21100

East Asian (EAS)

AF:

0.00

AC:

AN:

29552

South Asian (SAS)

AF:

0.00

AC:

AN:

62344

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5278

European-Non Finnish (NFE)

AF:

9.72e-7

AC:

AN:

1028374

Other (OTH)

AF:

0.000361

AC:

AN:

52690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00104

AC:

158

AN:

152038

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00357

AC:

148

AN:

41456

American (AMR)

AF:

0.000458

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67960

Other (OTH)

AF:

0.000951

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00121

Hom.:

Bravo

AF:

0.00114

ExAC

AF:

0.0000540

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

C2CD3-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.2

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.028

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.66

M_CAP

Benign

0.0014

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.63

PhyloP100

-0.27

PROVEAN

Benign

-0.52

REVEL

Benign

0.036

Sift

Benign

0.74

Sift4G

Benign

0.83

Vest4

0.058

MutPred

0.19

Gain of phosphorylation at N2327 (P = 0.0037)

MVP

0.085

ClinPred

0.017

GERP RS

-3.0

Varity_R

0.024

gMVP

0.26

Mutation Taster

=96/4

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over