chr14-91297293-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080414.4(CCDC88C):c.3966+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,608,290 control chromosomes in the GnomAD database, including 225,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24191 hom., cov: 33)

Exomes 𝑓: 0.52 ( 201724 hom. )

Consequence

CCDC88C
NM_001080414.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.328

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-91297293-C-T is Benign according to our data. Variant chr14-91297293-C-T is described in ClinVar as Benign. ClinVar VariationId is 158110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.3966+12G>A		intron_variant	Intron 22 of 29	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.3966+12G>A		intron_variant	Intron 22 of 29	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84557

AN:

152044

Hom.:

24177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.534

GnomAD2 exomes

AF:

0.498

AC:

119815

AN:

240752

AF XY:

0.488

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.549

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.522

AC:

760195

AN:

1456128

Hom.:

201724

Cov.:

AF XY:

0.515

AC XY:

372833

AN XY:

723756

show subpopulations

African (AFR)

AF:

0.672

AC:

22453

AN:

33390

American (AMR)

AF:

0.456

AC:

20061

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

13793

AN:

25964

East Asian (EAS)

AF:

0.431

AC:

17028

AN:

39552

South Asian (SAS)

AF:

0.308

AC:

26296

AN:

85252

European-Finnish (FIN)

AF:

0.558

AC:

29512

AN:

52928

Middle Eastern (MID)

AF:

0.518

AC:

2981

AN:

5760

European-Non Finnish (NFE)

AF:

0.538

AC:

596768

AN:

1109038

Other (OTH)

AF:

0.520

AC:

31303

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

18012

36024

54036

72048

90060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16976

33952

50928

67904

84880

<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:

0.556

AC:

84616

AN:

152162

Hom.:

24191

Cov.:

AF XY:

0.546

AC XY:

40613

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.672

AC:

27910

AN:

41532

American (AMR)

AF:

0.470

AC:

7178

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1854

AN:

3470

East Asian (EAS)

AF:

0.409

AC:

2113

AN:

5170

South Asian (SAS)

AF:

0.290

AC:

1398

AN:

4826

European-Finnish (FIN)

AF:

0.544

AC:

5752

AN:

10582

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.538

AC:

36595

AN:

67978

Other (OTH)

AF:

0.533

AC:

1126

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1928

3856

5783

7711

9639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.530

Hom.:

12499

Bravo

AF:

0.560

Asia WGS

AF:

0.379

AC:

1320

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

(source)

DANN

Benign

0.27

PhyloP100

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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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