rs11235979

Variant names:

• chr11-74028608-C-G
• rs11235979
• NM_001286577.2:c.6810-210G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-74028608-C-G
• chr11-74028608-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001286577.2(C2CD3):​c.6810-210G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 152,222 control chromosomes in the GnomAD database, including 898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.069 (898 hom., cov: 32)
• Consequence: C2CD3 NM_001286577.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.839
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-74028608-C-G is Benign according to our data. Variant chr11-74028608-C-G is described in ClinVar as Benign. ClinVar VariationId is 1281677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 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.6810-210G>C		intron	N/A	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.6810-210G>C		intron	N/A	ENSP00000334379.7	Q4AC94-5
	C2CD3	ENST00000680231.1		c.6810-210G>C		intron	N/A	ENSP00000505413.1	A0A7P0Z475
	C2CD3	ENST00000679906.1		c.6847+4705G>C		intron	N/A	ENSP00000505021.1	A0A7P0T883

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10463 AN: 152104 Hom.: 894 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0487

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

GnomAD4 genome AF: 0.0689 AC: 10491 AN: 152222 Hom.: 898 Cov.: 32 AF XY: 0.0673 AC XY: 5009 AN XY: 74430

African (AFR) AF: 0.201 AC: 8332 AN: 41482

American (AMR) AF: 0.0266 AC: 407 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.00810 AC: 42 AN: 5186

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4832

European-Finnish (FIN) AF: 0.0247 AC: 262 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1182 AN: 68028

Other (OTH) AF: 0.0496 AC: 105 AN: 2116

Alfa AF: 0.0105 Hom.: 7

Bravo AF: 0.0720

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11235979; hg19: chr11-73739653;