Variant 2-117975255-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_019044.5(CCDC93):c.683C>T(p.Pro228Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0717 in 1,612,948 control chromosomes in the GnomAD database, including 4,685 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.053 ( 286 hom., cov: 32)

Exomes 𝑓: 0.074 ( 4399 hom. )

Consequence

CCDC93
NM_019044.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.65

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017846525).

BP6

Variant 2-117975255-G-A is Benign according to our data. Variant chr2-117975255-G-A is described in ClinVar as [Benign]. Clinvar id is 1271261.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC93	NM_019044.5 linkuse as main transcript	c.683C>T	p.Pro228Leu	missense_variant	9/24	ENST00000376300.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCDC93	ENST00000376300.7 linkuse as main transcript	c.683C>T	p.Pro228Leu	missense_variant	9/24	1	NM_019044.5	P4
CCDC93	ENST00000319432.9 linkuse as main transcript	c.680C>T	p.Pro227Leu	missense_variant	9/24	5		A1
CCDC93	ENST00000460781.1 linkuse as main transcript	n.247C>T		non_coding_transcript_exon_variant	5/10	3

Frequencies

GnomAD3 genomes

AF:

0.0529

AC:

8050

AN:

152158

Hom.:

287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0352

Gnomad ASJ

AF:

0.0568

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0537

Gnomad FIN

AF:

0.0697

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0824

Gnomad OTH

AF:

0.0465

GnomAD3 exomes

AF:

0.0564

AC:

14154

AN:

250852

Hom.:

498

AF XY:

0.0587

AC XY:

7957

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.0298

Gnomad ASJ exome

AF:

0.0629

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0594

Gnomad FIN exome

AF:

0.0710

Gnomad NFE exome

AF:

0.0754

Gnomad OTH exome

AF:

0.0656

GnomAD4 exome

AF:

0.0736

AC:

107551

AN:

1460672

Hom.:

4399

Cov.:

AF XY:

0.0737

AC XY:

53592

AN XY:

726716

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.0307

Gnomad4 ASJ exome

AF:

0.0608

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0611

Gnomad4 FIN exome

AF:

0.0740

Gnomad4 NFE exome

AF:

0.0813

Gnomad4 OTH exome

AF:

0.0710

GnomAD4 genome

AF:

0.0528

AC:

8043

AN:

152276

Hom.:

286

Cov.:

AF XY:

0.0514

AC XY:

3829

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0568

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0535

Gnomad4 FIN

AF:

0.0697

Gnomad4 NFE

AF:

0.0824

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0724

Hom.:

924

Bravo

AF:

0.0481

TwinsUK

AF:

0.0871

AC:

323

ALSPAC

AF:

0.0771

AC:

297

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0809

AC:

696

ExAC

AF:

0.0571

AC:

6936

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0809

EpiControl

AF:

0.0759

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 23, 2021

This variant is associated with the following publications: (PMID: 31630160) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

Cadd

Benign

Dann

Benign

0.65

DEOGEN2

Benign

0.0032

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.064

Sift

Benign

0.062

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0070

B;.

Vest4

0.10

MPC

0.29

ClinPred

0.013

GERP RS

5.2

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Varity_R

0.059

gMVP

0.27

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

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