rs941920

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080414.4(CCDC88C):c.5975T>C(p.Leu1992Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,609,524 control chromosomes in the GnomAD database, including 629,801 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 61983 hom., cov: 34)

Exomes 𝑓: 0.88 ( 567818 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.254

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.007662E-7).

BP6

Variant 14-91272737-A-G is Benign according to our data. Variant chr14-91272737-A-G is described in ClinVar as [Benign]. Clinvar id is 158118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91272737-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.5975T>C	p.Leu1992Pro	missense_variant	Exon 30 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.5975T>C	p.Leu1992Pro	missense_variant	Exon 30 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1
CCDC88C	ENST00000556726 link	c.*1809T>C		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000452406.1		H0YJX5

Frequencies

GnomAD3 genomes

AF:

0.898

AC:

136665

AN:

152166

Hom.:

61928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.979

Gnomad AMI

AF:

0.901

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.731

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.870

GnomAD3 exomes

AF:

0.846

AC:

204013

AN:

241008

Hom.:

87667

AF XY:

0.844

AC XY:

111409

AN XY:

132042

show subpopulations

Gnomad AFR exome

AF:

0.981

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.861

Gnomad EAS exome

AF:

0.575

Gnomad SAS exome

AF:

0.751

Gnomad FIN exome

AF:

0.947

Gnomad NFE exome

AF:

0.896

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.880

AC:

1282470

AN:

1457240

Hom.:

567818

Cov.:

AF XY:

0.876

AC XY:

634881

AN XY:

724928

show subpopulations

Gnomad4 AFR exome

AF:

0.983

Gnomad4 AMR exome

AF:

0.792

Gnomad4 ASJ exome

AF:

0.863

Gnomad4 EAS exome

AF:

0.605

Gnomad4 SAS exome

AF:

0.748

Gnomad4 FIN exome

AF:

0.944

Gnomad4 NFE exome

AF:

0.899

Gnomad4 OTH exome

AF:

0.870

GnomAD4 genome

AF:

0.898

AC:

136779

AN:

152284

Hom.:

61983

Cov.:

AF XY:

0.893

AC XY:

66512

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.979

Gnomad4 AMR

AF:

0.818

Gnomad4 ASJ

AF:

0.855

Gnomad4 EAS

AF:

0.586

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.948

Gnomad4 NFE

AF:

0.898

Gnomad4 OTH

AF:

0.870

Alfa

AF:

0.882

Hom.:

105414

Bravo

AF:

0.894

TwinsUK

AF:

0.894

AC:

3314

ALSPAC

AF:

0.903

AC:

3480

ESP6500AA

AF:

0.976

AC:

3605

ESP6500EA

AF:

0.899

AC:

7322

ExAC

AF:

0.851

AC:

102108

Asia WGS

AF:

0.691

AC:

2406

AN:

3478

EpiCase

AF:

0.884

EpiControl

AF:

0.883

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 29, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Spinocerebellar ataxia type 40

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hydrocephalus, nonsyndromic, autosomal recessive 1

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

DANN

Benign

0.20

DEOGEN2

Benign

0.0020

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.073

T;T

MetaRNN

Benign

9.0e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

.;N

PrimateAI

Benign

0.28

PROVEAN

Benign

1.9

.;N

REVEL

Benign

0.0060

Sift

Benign

0.42

.;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

.;B

Vest4

0.017

MPC

0.21

ClinPred

0.0022

GERP RS

-2.6

Varity_R

0.043

gMVP

0.069

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