NM_001286577.2:c.6984G>T

Variant names:

• chr11-74013463-C-A
• rs61733219
• NM_001286577.2:c.6984G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001286577.2(C2CD3):​c.6984G>T​(p.Ser2328Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00658 in 1,427,474 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (30 hom.)
• Consequence: C2CD3 NM_001286577.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.42
• Publications: 0 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=-0.51).
• BP6: Variant 11-74013463-C-A is Benign according to our data. Variant chr11-74013463-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 778044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00566 (861/152218) while in subpopulation NFE AF = 0.00853 (580/68020). AF 95% confidence interval is 0.00795. There are 4 homozygotes in GnomAd4. There are 396 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.6984G>T	p.Ser2328Ser	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.6984G>T	p.Ser2328Ser	synonymous	Exon 33 of 33	ENSP00000334379.7	Q4AC94-5
	C2CD3	ENST00000681143.1		c.6579G>T	p.Ser2193Ser	synonymous	Exon 30 of 30	ENSP00000505970.1	A0A7P0Z4H1
	C2CD3	ENST00000923534.1		c.6489G>T	p.Ser2163Ser	synonymous	Exon 32 of 32	ENSP00000593593.1

Frequencies

GnomAD3 genomes AF: 0.00565 AC: 859 AN: 152100 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00291

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00853

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00439 AC: 264 AN: 60114 AF XY: 0.00444

Gnomad AFR exome AF: 0.000876

Gnomad AMR exome AF: 0.00319

Gnomad ASJ exome AF: 0.00491

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000240

Gnomad NFE exome AF: 0.00667

Gnomad OTH exome AF: 0.00923

GnomAD4 exome AF: 0.00669 AC: 8536 AN: 1275256 Hom.: 30 Cov.: 29 AF XY: 0.00667 AC XY: 4179 AN XY: 626950

African (AFR) AF: 0.00222 AC: 59 AN: 26580

American (AMR) AF: 0.00363 AC: 70 AN: 19300

Ashkenazi Jewish (ASJ) AF: 0.00616 AC: 130 AN: 21090

East Asian (EAS) AF: 0.00 AC: 0 AN: 29460

South Asian (SAS) AF: 0.00257 AC: 160 AN: 62272

European-Finnish (FIN) AF: 0.000929 AC: 29 AN: 31226

Middle Eastern (MID) AF: 0.0163 AC: 86 AN: 5280

European-Non Finnish (NFE) AF: 0.00748 AC: 7685 AN: 1027398

Other (OTH) AF: 0.00602 AC: 317 AN: 52650

GnomAD4 genome AF: 0.00566 AC: 861 AN: 152218 Hom.: 4 Cov.: 32 AF XY: 0.00532 AC XY: 396 AN XY: 74400

African (AFR) AF: 0.00137 AC: 57 AN: 41540

American (AMR) AF: 0.00752 AC: 115 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4814

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00853 AC: 580 AN: 68020

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00403 Hom.: 1

Bravo AF: 0.00600

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely 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	-0.51
CADD	Benign	0.55
DANN	Benign	0.77
PhyloP100		-1.4
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: rs61733219; hg19: chr11-73724508;