chr11-74028245-T-G

Variant names:

• chr11-74028245-T-G
• rs73555969
• NM_001286577.2:c.6921+42A>C

Variant summary

Our verdict is Benign. The variant received -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
• 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ENSG00000298570 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.6921+42A>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.6921+42A>C		intron	N/A	ENSP00000334379.7	Q4AC94-5
	C2CD3	ENST00000680231.1		c.6921+42A>C		intron	N/A	ENSP00000505413.1	A0A7P0Z475
	C2CD3	ENST00000679906.1		c.6847+5068A>C		intron	N/A	ENSP00000505021.1	A0A7P0T883

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

GnomAD2 exomes AF: 0.00417 AC: 541 AN: 129868 AF XY: 0.00315

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 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

African (AFR) AF: 0.0695 AC: 1934 AN: 27822

American (AMR) AF: 0.00355 AC: 121 AN: 34058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23522

East Asian (EAS) AF: 0.00 AC: 0 AN: 34876

South Asian (SAS) AF: 0.000295 AC: 22 AN: 74498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33678

Middle Eastern (MID) AF: 0.00226 AC: 12 AN: 5302

European-Non Finnish (NFE) AF: 0.0000469 AC: 43 AN: 916870

Other (OTH) AF: 0.00380 AC: 197 AN: 51842

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

African (AFR) AF: 0.0630 AC: 2614 AN: 41516

American (AMR) AF: 0.00647 AC: 99 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68008

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00283 Hom.: 3

Bravo AF: 0.0211

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.68
PhyloP100		-1.1
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: rs73555969; hg19: chr11-73739290;