2-130341845-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032357.4(CCDC115):c.211G>A(p.Ala71Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,570,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CCDC115
NM_032357.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.196

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053403914).

BP6

Variant 2-130341845-C-T is Benign according to our data. Variant chr2-130341845-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3138269.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC115	NM_032357.4 linkuse as main transcript	c.211G>A	p.Ala71Thr	missense_variant	2/5	ENST00000259229.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC115	ENST00000259229.7 linkuse as main transcript	c.211G>A	p.Ala71Thr	missense_variant	2/5	1	NM_032357.4	P1	Q96NT0-1

Frequencies

GnomAD3 genomes

AF:

0.0000411

AC:

AN:

145984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000761

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000375

AC:

AN:

240036

Hom.:

AF XY:

0.0000383

AC XY:

AN XY:

130596

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000747

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000337

AC:

AN:

1424638

Hom.:

Cov.:

AF XY:

0.0000381

AC XY:

AN XY:

709092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

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:

0.0000416

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000411

AC:

AN:

145984

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

70538

show subpopulations

Gnomad4 AFR

AF:

0.0000761

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.88

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

-0.24

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.15

Sift

Benign

0.99

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.21

MVP

0.75

MPC

0.25

ClinPred

0.031

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.43

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