rs17127255

chr14-91338035-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.1020C>T(p.His340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,613,004 control chromosomes in the GnomAD database, including 529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (291 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (238 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.860

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=-0.8).
• BP6: Variant 14-91338035-G-A is Benign according to our data. Variant chr14-91338035-G-A is described in ClinVar as [Benign]. Clinvar id is 158089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88C	NM_001080414.4	c.1020C>T	p.His340=	synonymous_variant	10/30	ENST00000389857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88C	ENST00000389857.11	c.1020C>T	p.His340=	synonymous_variant	10/30	5	NM_001080414.4	P1
CCDC88C	ENST00000554051.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4863 AN: 152168 Hom.: 290 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0253

GnomAD3 exomes AF: 0.00835 AC: 2074 AN: 248502 Hom.: 104 AF XY: 0.00643 AC XY: 867 AN XY: 134918

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00340

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000955

Gnomad NFE exome AF: 0.000443

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00329 AC: 4808 AN: 1460718 Hom.: 238 Cov.: 32 AF XY: 0.00283 AC XY: 2057 AN XY: 726734

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00202

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.000114

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.00663

GnomAD4 genome AF: 0.0320 AC: 4868 AN: 152286 Hom.: 291 Cov.: 33 AF XY: 0.0311 AC XY: 2314 AN XY: 74450

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0140 Hom.: 58

Bravo AF: 0.0371

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000593

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	Jan 31, 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	-0.80
Cadd	Benign	0.11
Dann	Benign	0.90

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: rs17127255; hg19: chr14-91804379;