rs17132572

Variant names:

• chr11-74013403-C-T
• rs17132572
• NM_001286577.2:c.7044G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001286577.2(C2CD3):​c.7044G>A​(p.Gln2348Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,204,038 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (76 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (51 hom.)
• Consequence: C2CD3 NM_001286577.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.205
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome type 14

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ENSG00000298570 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-74013403-C-T is Benign according to our data. Variant chr11-74013403-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.205 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.059 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286577.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD3	NM_001286577.2	MANE Select	c.7044G>A	p.Gln2348Gln	synonymous	Exon 33 of 33	NP_001273506.1	Q4AC94-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD3	ENST00000334126.12	TSL:5 MANE Select	c.7044G>A	p.Gln2348Gln	synonymous	Exon 33 of 33	ENSP00000334379.7	Q4AC94-5
	C2CD3	ENST00000681143.1		c.6639G>A	p.Gln2213Gln	synonymous	Exon 30 of 30	ENSP00000505970.1	A0A7P0Z4H1
	C2CD3	ENST00000923534.1		c.6549G>A	p.Gln2183Gln	synonymous	Exon 32 of 32	ENSP00000593593.1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2662 AN: 152098 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00364 AC: 123 AN: 33814 AF XY: 0.00218

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.00302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00162 AC: 1704 AN: 1051822 Hom.: 51 Cov.: 13 AF XY: 0.00150 AC XY: 780 AN XY: 520392

African (AFR) AF: 0.0660 AC: 1430 AN: 21680

American (AMR) AF: 0.00459 AC: 63 AN: 13740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17352

East Asian (EAS) AF: 0.00 AC: 0 AN: 27774

South Asian (SAS) AF: 0.0000804 AC: 4 AN: 49750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29510

Middle Eastern (MID) AF: 0.00190 AC: 9 AN: 4742

European-Non Finnish (NFE) AF: 0.0000439 AC: 37 AN: 842490

Other (OTH) AF: 0.00360 AC: 161 AN: 44784

GnomAD4 genome AF: 0.0175 AC: 2666 AN: 152216 Hom.: 76 Cov.: 32 AF XY: 0.0173 AC XY: 1286 AN XY: 74444

African (AFR) AF: 0.0609 AC: 2530 AN: 41518

American (AMR) AF: 0.00640 AC: 98 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68004

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00970 Hom.: 17

Bravo AF: 0.0205

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.55
DANN	Benign	0.70
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs17132572; hg19: chr11-73724448;