chr11-74028045-T-C

Position:

• chr11-74028045-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001286577.2(C2CD3):​c.6921+242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 152,184 control chromosomes in the GnomAD database, including 854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.060 (854 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-74028045-T-C is Benign according to our data. Variant chr11-74028045-T-C is described in ClinVar as [Benign]. Clinvar id is 1238733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.6921+242A>G		intron_variant		ENST00000334126.12	NP_001273506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12	c.6921+242A>G		intron_variant		5	NM_001286577.2	ENSP00000334379.7

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9077 AN: 152066 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.0435

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0598 AC: 9102 AN: 152184 Hom.: 854 Cov.: 32 AF XY: 0.0580 AC XY: 4314 AN XY: 74436

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00432

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0404 Hom.: 67

Bravo AF: 0.0652

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.60
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1685343; hg19: chr11-73739090;