rs45542736

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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=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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.5948G>C	p.Gly1983Ala	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.5948G>C	p.Gly1983Ala	missense_variant	Exon 30 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1
CCDC88C	ENST00000556726 link	c.*1782G>C		3_prime_UTR_variant	Exon 7 of 7	5		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

GnomAD3 exomes

AF:

0.0189

AC:

4534

AN:

240012

Hom.:

AF XY:

0.0198

AC XY:

2606

AN XY:

131408

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 SAS exome

AF:

0.0226

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

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0332

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0216

Gnomad4 FIN exome

AF:

0.0531

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0177

GnomAD4 genome

AF:

0.0153

AC:

2337

AN:

152334

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1326

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0226

Gnomad4 FIN

AF:

0.0702

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.0194

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

Significance: Benign

Submissions summary: Benign:4

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

- -

May 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.042

Sift

Benign

0.51

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.13

.;B

Vest4

0.018

MPC

0.16

ClinPred

0.0057

GERP RS

2.7

Varity_R

0.067

gMVP

0.15

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