11-74088255-C-T

Position:

• chr11-74088255-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286577.2(C2CD3):​c.3642-2369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,112 control chromosomes in the GnomAD database, including 30,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (30176 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2CD3	NM_001286577.2	c.3642-2369G>A		intron_variant		ENST00000334126.12
C2CD3	NM_015531.6	c.3642-2369G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2CD3	ENST00000334126.12	c.3642-2369G>A		intron_variant		5	NM_001286577.2	P2

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92298 AN: 151996 Hom.: 30127 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.607 AC: 92405 AN: 152112 Hom.: 30176 Cov.: 32 AF XY: 0.607 AC XY: 45102 AN XY: 74356

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.553

Alfa AF: 0.418 Hom.: 1081

Bravo AF: 0.610

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs826056; hg19: chr11-73799300;