chr11-74028245-T-G

Position:

• chr11-74028245-T-G

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+42A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,354,678 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (80 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (79 hom.)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11

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=-0.88).
• BP6: Variant 11-74028245-T-G is Benign according to our data. Variant chr11-74028245-T-G is described in ClinVar as [Benign]. Clinvar id is 1273538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.6921+42A>C		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+42A>C		intron_variant		5	NM_001286577.2	ENSP00000334379.7

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2745 AN: 152092 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00417 AC: 541 AN: 129868 Hom.: 19 AF XY: 0.00315 AC XY: 222 AN XY: 70588

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000790

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.00194 AC: 2329 AN: 1202468 Hom.: 79 Cov.: 16 AF XY: 0.00172 AC XY: 1037 AN XY: 601750

Gnomad4 AFR exome AF: 0.0695

Gnomad4 AMR exome AF: 0.00355

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000295

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000469

Gnomad4 OTH exome AF: 0.00380

GnomAD4 genome AF: 0.0181 AC: 2750 AN: 152210 Hom.: 80 Cov.: 32 AF XY: 0.0176 AC XY: 1308 AN XY: 74440

Gnomad4 AFR AF: 0.0630

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.0211

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

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73555969; hg19: chr11-73739290;