14-91307224-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080414.4(CCDC88C):c.3009A>G(p.Leu1003Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,612,236 control chromosomes in the GnomAD database, including 260,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23643 hom., cov: 32)

Exomes 𝑓: 0.57 ( 237164 hom. )

Consequence

CCDC88C
NM_001080414.4 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0160

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 14-91307224-T-C is Benign according to our data. Variant chr14-91307224-T-C is described in ClinVar as [Benign]. Clinvar id is 158098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91307224-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.016 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.3009A>G	p.Leu1003Leu	splice_region_variant, synonymous_variant	Exon 18 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.3009A>G	p.Leu1003Leu	splice_region_variant, synonymous_variant	Exon 18 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84312

AN:

151984

Hom.:

23633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.532

AC:

132116

AN:

248246

Hom.:

36192

AF XY:

0.526

AC XY:

70862

AN XY:

134842

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.518

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.367

Gnomad SAS exome

AF:

0.388

Gnomad FIN exome

AF:

0.626

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.566

AC:

826433

AN:

1460134

Hom.:

237164

Cov.:

AF XY:

0.560

AC XY:

406632

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.542

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.509

Gnomad4 EAS exome

AF:

0.395

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.589

Gnomad4 OTH exome

AF:

0.544

GnomAD4 genome

AF:

0.555

AC:

84369

AN:

152102

Hom.:

23643

Cov.:

AF XY:

0.549

AC XY:

40805

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.548

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.521

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.390

Gnomad4 FIN

AF:

0.633

Gnomad4 NFE

AF:

0.588

Gnomad4 OTH

AF:

0.520

Alfa

AF:

0.565

Hom.:

29721

Bravo

AF:

0.545

Asia WGS

AF:

0.399

AC:

1393

AN:

3478

EpiCase

AF:

0.567

EpiControl

AF:

0.565

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

- -

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

-0.59

CADD

Benign

4.0

DANN

Benign

0.36

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