rs534735031

Variant names:

• chr11-74013456-G-A
• rs534735031
• NM_001286577.2:c.6991C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-74013456-G-A
• chr11-74013456-G-C
• chr11-74013456-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286577.2(C2CD3):​c.6991C>T​(p.Leu2331Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,432,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: C2CD3 NM_001286577.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.133
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14886615).

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.6991C>T	p.Leu2331Phe	missense	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.6991C>T	p.Leu2331Phe	missense	Exon 33 of 33	ENSP00000334379.7	Q4AC94-5
	C2CD3	ENST00000681143.1		c.6586C>T	p.Leu2196Phe	missense	Exon 30 of 30	ENSP00000505970.1	A0A7P0Z4H1
	C2CD3	ENST00000923534.1		c.6496C>T	p.Leu2166Phe	missense	Exon 32 of 32	ENSP00000593593.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 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: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1280738 Hom.: 0 Cov.: 28 AF XY: 0.00000159 AC XY: 1 AN XY: 630012

African (AFR) AF: 0.00 AC: 0 AN: 26760

American (AMR) AF: 0.00 AC: 0 AN: 20068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21400

East Asian (EAS) AF: 0.00 AC: 0 AN: 29646

South Asian (SAS) AF: 0.00 AC: 0 AN: 63336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029836

Other (OTH) AF: 0.0000378 AC: 2 AN: 52960

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.090
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.13
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.039
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.016	D
Vest4		0.071
MutPred		0.28		Loss of catalytic residue at L2331 (P = 0.1097)
MVP		0.42
ClinPred		0.88	D
GERP RS		4.6
Varity_R		0.049
gMVP		0.15
Mutation Taster		=96/4	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs534735031; hg19: chr11-73724501;