Variant chr2-130340932-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_032357.4(CCDC115):c.406C>G(p.Gln136Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000202 in 1,614,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

CCDC115
NM_032357.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.79

Variant links:

Genes affected

CCDC115 (HGNC:28178): (coiled-coil domain containing 115) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) vesicles in some human cells. The encoded protein shares some homology with the yeast V-ATPase assembly factor Vma22p, and the orthologous protein in mouse promotes cell proliferation and suppresses cell death. Defects in this gene are a cause of congenital disorder of glycosylation, type IIo in humans. [provided by RefSeq, Mar 2016]

CCDC115 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014177889).

BP6

Variant 2-130340932-G-C is Benign according to our data. Variant chr2-130340932-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2158172.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC115	NM_032357.4 linkuse as main transcript	c.406C>G	p.Gln136Glu	missense_variant	4/5	ENST00000259229.7	NP_115733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC115	ENST00000259229.7 linkuse as main transcript	c.406C>G	p.Gln136Glu	missense_variant	4/5	1	NM_032357.4	ENSP00000259229	P1	Q96NT0-1

Frequencies

GnomAD3 genomes

AF:

0.000959

AC:

146

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000279

AC:

AN:

251260

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00340

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000121

AC:

177

AN:

1461814

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000978

AC:

149

AN:

152302

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00318

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 25, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.097

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

D;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.014

T;T

MetaSVM

Uncertain

0.65

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

0.73

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.45

Sift

Benign

0.036

D;D

Sift4G

Uncertain

0.042

D;D

Polyphen

0.25

B;P

Vest4

0.46

MVP

0.96

MPC

0.50

ClinPred

0.087

GERP RS

3.6

Varity_R

0.17

gMVP

0.59

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