Variant 11-74028256-T-C 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.6921+31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,422,116 control chromosomes in the GnomAD database, including 1,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 827 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 730 hom. )

Consequence

C2CD3
NM_001286577.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.28

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:

C2CD3 (HGNC:):

C2CD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-74028256-T-C is Benign according to our data. Variant chr11-74028256-T-C is described in ClinVar as [Benign]. Clinvar id is 1271346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 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.6921+31A>G		intron_variant		ENST00000334126.12	NP_001273506.1	Q4AC94-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12 linkuse as main transcript	c.6921+31A>G		intron_variant		5	NM_001286577.2	ENSP00000334379.7		Q4AC94-5

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8798

AN:

152048

Hom.:

821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0205

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0134

AC:

1797

AN:

134172

Hom.:

135

AF XY:

0.0106

AC XY:

773

AN XY:

72944

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.0000957

Gnomad SAS exome

AF:

0.000453

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000858

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00676

AC:

8582

AN:

1269950

Hom.:

730

Cov.:

AF XY:

0.00587

AC XY:

3712

AN XY:

632354

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.0000284

Gnomad4 SAS exome

AF:

0.000665

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000495

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0580

AC:

8833

AN:

152166

Hom.:

827

Cov.:

AF XY:

0.0553

AC XY:

4113

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.0205

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.0398

Alfa

AF:

0.0275

Hom.:

Bravo

AF:

0.0655

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.037

DANN

Benign

0.62

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