chr18-54919288-G-C

Position:

• chr18-54919288-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025214.3(CCDC68):​c.772C>G​(p.Arg258Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC68 NM_025214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

Genes affected

CCDC68 (HGNC:24350): (coiled-coil domain containing 68) Involved in microtubule anchoring at centrosome and protein localization. Located in centriole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC68	NM_025214.3	c.772C>G	p.Arg258Gly	missense_variant	9/12	ENST00000591504.6	NP_079490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC68	ENST00000591504.6	c.772C>G	p.Arg258Gly	missense_variant	9/12	1	NM_025214.3	ENSP00000466690.1
CCDC68	ENST00000432185.5	c.772C>G	p.Arg258Gly	missense_variant	7/10	1		ENSP00000413406.1
CCDC68	ENST00000337363.8	c.772C>G	p.Arg258Gly	missense_variant	9/12	2		ENSP00000337209.3
CCDC68	ENST00000592040.5	c.373C>G	p.Arg125Gly	missense_variant	4/8	3		ENSP00000466731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460876 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2022

The c.772C>G (p.R258G) alteration is located in exon 9 (coding exon 7) of the CCDC68 gene. This alteration results from a C to G substitution at nucleotide position 772, causing the arginine (R) at amino acid position 258 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	.;T;.
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.9	M;M;M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.1	.;D;D
REVEL	Benign	0.085
Sift	Uncertain	0.012	.;D;D
Sift4G	Benign	0.072	T;T;T
Polyphen		0.71	P;P;P
Vest4		0.75
MutPred		0.22		Loss of MoRF binding (P = 0.0671);Loss of MoRF binding (P = 0.0671);Loss of MoRF binding (P = 0.0671);
MVP		0.17
MPC		0.19
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.25
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-52586519;