14-91325976-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080414.4(CCDC88C):c.1131C>T(p.Gly377Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 1,582,512 control chromosomes in the GnomAD database, including 2,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 293 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2072 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.13

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

hydrocephalus, nonsyndromic, autosomal recessive 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
spinocerebellar ataxia type 40
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

CCDC88C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-91325976-G-A is Benign according to our data. Variant chr14-91325976-G-A is described in ClinVar as [Benign]. Clinvar id is 158105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.1131C>T	p.Gly377Gly	synonymous_variant	Exon 11 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.1131C>T	p.Gly377Gly	synonymous_variant	Exon 11 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8661

AN:

151944

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0721

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0399

Gnomad ASJ

AF:

0.0701

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0357

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0446

Gnomad OTH

AF:

0.0603

GnomAD2 exomes

AF:

0.0570

AC:

11553

AN:

202604

AF XY:

0.0587

show subpopulations

Gnomad AFR exome

AF:

0.0744

Gnomad AMR exome

AF:

0.0264

Gnomad ASJ exome

AF:

0.0631

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.0347

Gnomad NFE exome

AF:

0.0451

Gnomad OTH exome

AF:

0.0506

GnomAD4 exome

AF:

0.0489

AC:

70020

AN:

1430448

Hom.:

2072

Cov.:

AF XY:

0.0504

AC XY:

35728

AN XY:

708576

show subpopulations

African (AFR)

AF:

0.0731

AC:

2398

AN:

32810

American (AMR)

AF:

0.0279

AC:

1107

AN:

39684

Ashkenazi Jewish (ASJ)

AF:

0.0576

AC:

1472

AN:

25540

East Asian (EAS)

AF:

0.116

AC:

4465

AN:

38426

South Asian (SAS)

AF:

0.0907

AC:

7445

AN:

82040

European-Finnish (FIN)

AF:

0.0358

AC:

1845

AN:

51484

Middle Eastern (MID)

AF:

0.0666

AC:

382

AN:

5736

European-Non Finnish (NFE)

AF:

0.0434

AC:

47523

AN:

1095442

Other (OTH)

AF:

0.0571

AC:

3383

AN:

59286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

3308

6616

9925

13233

16541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1886

3772

5658

7544

9430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0570

AC:

8667

AN:

152064

Hom.:

293

Cov.:

AF XY:

0.0572

AC XY:

4252

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0722

AC:

2994

AN:

41454

American (AMR)

AF:

0.0398

AC:

609

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0701

AC:

243

AN:

3468

East Asian (EAS)

AF:

0.143

AC:

739

AN:

5176

South Asian (SAS)

AF:

0.101

AC:

485

AN:

4818

European-Finnish (FIN)

AF:

0.0357

AC:

377

AN:

10568

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0446

AC:

3029

AN:

67978

Other (OTH)

AF:

0.0592

AC:

125

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

399

798

1197

1596

1995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0488

Hom.:

481

Bravo

AF:

0.0575

Asia WGS

AF:

0.109

AC:

376

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

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

- -

not specified

Benign:1

Apr 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.68

(source)

DANN

Benign

0.48

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over