2-117948106-C-T

Position:

chr2-117948106-C-T

Variant summary

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

The NM_019044.5(CCDC93):c.1223G>A(p.Arg408Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000932 in 1,610,256 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CCDC93
NM_019044.5 missense, splice_region

Scores

Splicing: ADA: 0.9626

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

Variant links:

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 links:

CCDC93 (HGNC:):

CCDC93 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
CCDC93	NM_019044.5 linkuse as main transcript	c.1223G>A	p.Arg408Gln	missense_variant, splice_region_variant	15/24	ENST00000376300.7	NP_061917.3	Q567U6
CCDC93	XM_011511359.2 linkuse as main transcript	c.1220G>A	p.Arg407Gln	missense_variant, splice_region_variant	15/24		XP_011509661.2
CCDC93	XM_011511361.1 linkuse as main transcript	c.935G>A	p.Arg312Gln	missense_variant, splice_region_variant	14/23		XP_011509663.1
CCDC93	XM_047444816.1 linkuse as main transcript	c.824G>A	p.Arg275Gln	missense_variant, splice_region_variant	12/21		XP_047300772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC93	ENST00000376300.7 linkuse as main transcript	c.1223G>A	p.Arg408Gln	missense_variant, splice_region_variant	15/24	1	NM_019044.5	ENSP00000365477.2	Q567U6
CCDC93	ENST00000319432.9 linkuse as main transcript	c.1220G>A	p.Arg407Gln	missense_variant, splice_region_variant	15/24	5		ENSP00000324135.5	F8W9X7
CCDC93	ENST00000437999.5 linkuse as main transcript	n.74G>A		splice_region_variant, non_coding_transcript_exon_variant	1/11	3		ENSP00000392989.1	H7C050
CCDC93	ENST00000488908.1 linkuse as main transcript	n.195G>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251108

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1458060

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725648

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000722

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.1223G>A (p.R408Q) alteration is located in exon 15 (coding exon 15) of the CCDC93 gene. This alteration results from a G to A substitution at nucleotide position 1223, causing the arginine (R) at amino acid position 408 to be replaced by a glutamine (Q). 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

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.0058

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.097

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.98

D;.

Vest4

0.70

MutPred

0.18

Loss of MoRF binding (P = 0.1121);.;

MVP

0.43

MPC

0.55

ClinPred

0.56

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over