rs17127245

chr14-91325976-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080414.4(CCDC88C):c.1131C>T(p.Gly377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 1,582,512 control chromosomes in the GnomAD database, including 2,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (293 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2072 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-91325976-G-A is Benign according to our data. Variant chr14-91325976-G-A is described in ClinVar as [Benign]. Clinvar id is 158105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88C	NM_001080414.4	c.1131C>T	p.Gly377=	synonymous_variant	11/30	ENST00000389857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88C	ENST00000389857.11	c.1131C>T	p.Gly377=	synonymous_variant	11/30	5	NM_001080414.4	P1

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8661 AN: 151944 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0603

GnomAD3 exomes AF: 0.0570 AC: 11553 AN: 202604 Hom.: 471 AF XY: 0.0587 AC XY: 6397 AN XY: 108890

Gnomad AFR exome AF: 0.0744

Gnomad AMR exome AF: 0.0264

Gnomad ASJ exome AF: 0.0631

Gnomad EAS exome AF: 0.140

Gnomad SAS exome AF: 0.0924

Gnomad FIN exome AF: 0.0347

Gnomad NFE exome AF: 0.0451

Gnomad OTH exome AF: 0.0506

GnomAD4 exome AF: 0.0489 AC: 70020 AN: 1430448 Hom.: 2072 Cov.: 31 AF XY: 0.0504 AC XY: 35728 AN XY: 708576

Gnomad4 AFR exome AF: 0.0731

Gnomad4 AMR exome AF: 0.0279

Gnomad4 ASJ exome AF: 0.0576

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.0907

Gnomad4 FIN exome AF: 0.0358

Gnomad4 NFE exome AF: 0.0434

Gnomad4 OTH exome AF: 0.0571

GnomAD4 genome AF: 0.0570 AC: 8667 AN: 152064 Hom.: 293 Cov.: 32 AF XY: 0.0572 AC XY: 4252 AN XY: 74336

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0446

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0480 Hom.: 156

Bravo AF: 0.0575

Asia WGS AF: 0.109 AC: 376 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.68
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs17127245; hg19: chr14-91792320; COSMIC: COSV66240703;