chr2-117958478-A-G

Position:

• chr2-117958478-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_019044.5(CCDC93):​c.892T>C​(p.Ser298Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC93 NM_019044.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58

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 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity CCD93_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC93	NM_019044.5	c.892T>C	p.Ser298Pro	missense_variant	12/24	ENST00000376300.7	NP_061917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC93	ENST00000376300.7	c.892T>C	p.Ser298Pro	missense_variant	12/24	1	NM_019044.5	ENSP00000365477.2
CCDC93	ENST00000319432.9	c.889T>C	p.Ser297Pro	missense_variant	12/24	5		ENSP00000324135.5
CCDC93	ENST00000460781.1	n.453T>C		splice_region_variant, non_coding_transcript_exon_variant	8/10	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jun 04, 2024

The c.892T>C (p.S298P) alteration is located in exon 12 (coding exon 12) of the CCDC93 gene. This alteration results from a T to C substitution at nucleotide position 892, causing the serine (S) at amino acid position 298 to be replaced by a proline (P). 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	0.56
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	0.016
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;.
MutationTaster	Benign	0.58	N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.17
Sift	Benign	0.031	D;D
Sift4G	Benign	0.23	T;T
Polyphen		0.94	P;.
Vest4		0.63
MutPred		0.18		Loss of phosphorylation at S298 (P = 0.023);.;
MVP		0.40
MPC		0.41
ClinPred		0.60	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1040756389; hg19: chr2-118716054;