11-74028393-C-T

Variant names:

• chr11-74028393-C-T
• rs1056578921
• NM_001286577.2:c.6815G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286577.2(C2CD3):​c.6815G>A​(p.Gly2272Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 1,534,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: C2CD3 NM_001286577.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0672988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD3	NM_001286577.2	c.6815G>A	p.Gly2272Glu	missense_variant	Exon 32 of 33	ENST00000334126.12	NP_001273506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD3	ENST00000334126.12	c.6815G>A	p.Gly2272Glu	missense_variant	Exon 32 of 33	5	NM_001286577.2	ENSP00000334379.7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000362 AC: 5 AN: 1382510 Hom.: 0 Cov.: 29 AF XY: 0.00000440 AC XY: 3 AN XY: 682288

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74298

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Benign	0.32
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.3	N
PROVEAN	Benign	1.3	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.15
MutPred		0.17		Gain of disorder (P = 0.0838);
MVP		0.45
ClinPred		0.11	T
GERP RS		4.4
Varity_R		0.031
gMVP		0.085

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1056578921; hg19: chr11-73739438;