2-117975255-G-C

Position:

• chr2-117975255-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019044.5(CCDC93):​c.683C>G​(p.Pro228Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P228L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC93 NM_019044.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.65

Genes affected

CCDC93 (HGNC:25611): (coiled-coil domain containing 93) Involved in Golgi to plasma membrane transport and endocytic recycling. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

CCDC93 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13291776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC93	NM_019044.5	c.683C>G	p.Pro228Arg	missense_variant	9/24	ENST00000376300.7	NP_061917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC93	ENST00000376300.7	c.683C>G	p.Pro228Arg	missense_variant	9/24	1	NM_019044.5	ENSP00000365477.2
CCDC93	ENST00000319432.9	c.680C>G	p.Pro227Arg	missense_variant	9/24	5		ENSP00000324135.5
CCDC93	ENST00000460781.1	n.247C>G		non_coding_transcript_exon_variant	5/10	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.0040	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.042
Sift	Benign	0.087	T;D
Sift4G	Benign	0.50	T;T
Polyphen		0.017	B;.
Vest4		0.28
MutPred		0.24		Gain of MoRF binding (P = 2e-04);.;
MVP		0.51
MPC		0.30
ClinPred		0.15	T
GERP RS		5.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
Varity_R		0.071
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17512204; hg19: chr2-118732831;