rs61743881

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001080414.4(CCDC88C):c.2456A>G(p.Asp819Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00137 in 1,611,430 control chromosomes in the GnomAD database, including 3 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 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:3

Conservation

PhyloP100: 4.06

Variant links:

Genes affected

CCDC88C (HGNC:19967): (coiled-coil domain containing 88C) This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation of the Wnt signaling pathway. The Wnt signaling pathway plays an important role in embryonic development, tissue maintenance, and cancer progression. Mutations in this gene cause autosomal recessive, primary non-syndromic congenital hydrocephalus; a condition characterized by excessive accumulation of cerebrospinal fluid in the ventricles of the brain. [provided by RefSeq, Jan 2013]

CCDC88C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009338051).

BP6

Variant 14-91313360-T-C is Benign according to our data. Variant chr14-91313360-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158097.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.2456A>G	p.Asp819Gly	missense_variant	Exon 15 of 30	ENST00000389857.11	NP_001073883.2	Q9P219-1B4DZB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 link	c.2456A>G	p.Asp819Gly	missense_variant	Exon 15 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00110

AC:

270

AN:

246534

Hom.:

AF XY:

0.000925

AC XY:

124

AN XY:

134092

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00149

Gnomad OTH exome

AF:

0.000995

GnomAD4 exome

AF:

0.00141

AC:

2051

AN:

1459114

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

996

AN XY:

726026

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00164

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152316

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00132

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000707

AC:

ESP6500EA

AF:

0.00295

AC:

ExAC

AF:

0.000999

AC:

121

EpiCase

AF:

0.00262

EpiControl

AF:

0.00196

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:4Benign:1

Mar 12, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 01, 2021

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

May 24, 2017

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CCDC88C-related disorder

Benign:1

May 22, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.023

MetaRNN

Benign

0.0093

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.092

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.66

Vest4

0.34

MVP

0.57

MPC

0.28

ClinPred

0.058

GERP RS

4.9

Varity_R

0.25

gMVP

0.26

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