14-91273058-C-T

Position:

chr14-91273058-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001080414.4(CCDC88C):c.5654G>A(p.Arg1885His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,556,670 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.34

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=0.007236898).

BP6

Variant 14-91273058-C-T is Benign according to our data. Variant chr14-91273058-C-T is described in ClinVar as [Benign]. Clinvar id is 158115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91273058-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00244 (372/152306) while in subpopulation AFR AF= 0.00842 (350/41568). AF 95% confidence interval is 0.00769. There are 2 homozygotes in gnomad4. There are 173 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC88C	NM_001080414.4 linkuse as main transcript	c.5654G>A	p.Arg1885His	missense_variant	30/30	ENST00000389857.11	NP_001073883.2
CCDC88C	XM_011536796.3 linkuse as main transcript	c.5546G>A	p.Arg1849His	missense_variant	30/30		XP_011535098.1
CCDC88C	XM_047431418.1 linkuse as main transcript	c.5387G>A	p.Arg1796His	missense_variant	27/27		XP_047287374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 linkuse as main transcript	c.5654G>A	p.Arg1885His	missense_variant	30/30	5	NM_001080414.4	ENSP00000374507	P1	Q9P219-1
CCDC88C	ENST00000556726.5 linkuse as main transcript	c.*1488G>A		3_prime_UTR_variant	7/7	5		ENSP00000452406

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

370

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00840

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000582

AC:

AN:

159856

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

87514

show subpopulations

Gnomad AFR exome

AF:

0.00801

Gnomad AMR exome

AF:

0.000644

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000813

Gnomad SAS exome

AF:

0.0000420

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.000678

GnomAD4 exome

AF:

0.000273

AC:

384

AN:

1404364

Hom.:

Cov.:

AF XY:

0.000245

AC XY:

170

AN XY:

693242

show subpopulations

Gnomad4 AFR exome

AF:

0.00819

Gnomad4 AMR exome

AF:

0.000744

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000622

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000406

Gnomad4 OTH exome

AF:

0.000721

GnomAD4 genome

AF:

0.00244

AC:

372

AN:

152306

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00842

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000295

Hom.:

Bravo

AF:

0.00305

ESP6500AA

AF:

0.00570

AC:

ESP6500EA

AF:

0.000644

AC:

ExAC

AF:

0.000523

AC:

Asia WGS

AF:

0.00115

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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 08, 2013

- -

CCDC88C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 19, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0072

T;T

MetaSVM

Uncertain

-0.057

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.3

.;N

REVEL

Uncertain

0.40

Sift

Uncertain

0.0040

.;D

Sift4G

Benign

0.15

T;D

Polyphen

1.0

.;D

Vest4

0.39

MVP

0.81

MPC

0.67

ClinPred

0.036

GERP RS

5.1

Varity_R

0.23

gMVP

0.22

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