rs45542736

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001080414.4(CCDC88C):c.5948G>C(p.Gly1983Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,607,908 control chromosomes in the GnomAD database, including 342 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 39 hom., cov: 32)

Exomes 𝑓: 0.017 ( 303 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.38

Publications

6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
spinocerebellar ataxia type 40
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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 (MetaRNN=0.0019318163).

BP6

Variant 14-91272764-C-G is Benign according to our data. Variant chr14-91272764-C-G is described in ClinVar as Benign. ClinVar VariationId is 158116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0153 (2337/152334) while in subpopulation SAS AF = 0.0226 (109/4830). AF 95% confidence interval is 0.0191. There are 39 homozygotes in GnomAd4. There are 1326 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080414.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC88C	NM_001080414.4	MANE Select	c.5948G>C	p.Gly1983Ala	missense	Exon 30 of 30	NP_001073883.2	Q9P219-1
CCDC88C	NR_189158.1		n.6225G>C		non_coding_transcript_exon	Exon 31 of 31
CCDC88C	NR_189159.1		n.6520G>C		non_coding_transcript_exon	Exon 31 of 31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.5948G>C	p.Gly1983Ala	missense	Exon 30 of 30	ENSP00000374507.6	Q9P219-1
	CCDC88C	ENST00000556726.5	TSL:5	c.*1782G>C		3_prime_UTR	Exon 7 of 7	ENSP00000452406.1	H0YJX5

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2340

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0702

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.0189

AC:

4534

AN:

240012

AF XY:

0.0198

show subpopulations

Gnomad AFR exome

AF:

0.00204

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.0316

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.0618

Gnomad NFE exome

AF:

0.0167

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0172

AC:

25079

AN:

1455574

Hom.:

303

Cov.:

AF XY:

0.0174

AC XY:

12579

AN XY:

723968

show subpopulations

African (AFR)

AF:

0.00239

AC:

AN:

33442

American (AMR)

AF:

0.0119

AC:

531

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.0332

AC:

865

AN:

26032

East Asian (EAS)

AF:

0.000126

AC:

AN:

39646

South Asian (SAS)

AF:

0.0216

AC:

1858

AN:

85994

European-Finnish (FIN)

AF:

0.0531

AC:

2625

AN:

49444

Middle Eastern (MID)

AF:

0.0256

AC:

146

AN:

5714

European-Non Finnish (NFE)

AF:

0.0161

AC:

17905

AN:

1110532

Other (OTH)

AF:

0.0177

AC:

1064

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1471

2942

4412

5883

7354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.0153

AC:

2337

AN:

152334

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1326

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00255

AC:

106

AN:

41588

American (AMR)

AF:

0.0115

AC:

176

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0226

AC:

109

AN:

4830

European-Finnish (FIN)

AF:

0.0702

AC:

745

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0155

AC:

1052

AN:

68026

Other (OTH)

AF:

0.0194

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

115

231

346

462

577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0154

Hom.:

Bravo

AF:

0.0108

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.00187

AC:

ESP6500EA

AF:

0.0154

AC:

126

ExAC

AF:

0.0179

AC:

2156

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.032

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

PhyloP100

1.4

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

REVEL

Benign

0.042

Sift

Benign

0.51

Sift4G

Benign

1.0

Polyphen

0.13

Vest4

0.018

MPC

0.16

ClinPred

0.0057

GERP RS

2.7

Varity_R

0.067

gMVP

0.15

Mutation Taster

=94/6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over