rs61736349

chr14-91338143-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001080414.4(CCDC88C):c.912C>T(p.Asp304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,613,808 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (44 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.510

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=-0.71).
• BP6: Variant 14-91338143-G-A is Benign according to our data. Variant chr14-91338143-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 158128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00431 (656/152328) while in subpopulation NFE AF= 0.00725 (493/68034). AF 95% confidence interval is 0.00672. There are 3 homozygotes in gnomad4. There are 279 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88C	NM_001080414.4	c.912C>T	p.Asp304=	synonymous_variant	10/30	ENST00000389857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88C	ENST00000389857.11	c.912C>T	p.Asp304=	synonymous_variant	10/30	5	NM_001080414.4	P1
CCDC88C	ENST00000554051.1	n.389C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00431 AC: 656 AN: 152210 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00725

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00420 AC: 1045 AN: 248686 Hom.: 4 AF XY: 0.00423 AC XY: 571 AN XY: 134976

Gnomad AFR exome AF: 0.00188

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00289

Gnomad EAS exome AF: 0.000223

Gnomad SAS exome AF: 0.000981

Gnomad FIN exome AF: 0.00372

Gnomad NFE exome AF: 0.00714

Gnomad OTH exome AF: 0.00348

GnomAD4 exome AF: 0.00627 AC: 9168 AN: 1461480 Hom.: 44 Cov.: 32 AF XY: 0.00611 AC XY: 4440 AN XY: 727028

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00329

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000858

Gnomad4 FIN exome AF: 0.00417

Gnomad4 NFE exome AF: 0.00754

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome AF: 0.00431 AC: 656 AN: 152328 Hom.: 3 Cov.: 33 AF XY: 0.00375 AC XY: 279 AN XY: 74476

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00725

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00563 Hom.: 4

Bravo AF: 0.00400

EpiCase AF: 0.00573

EpiControl AF: 0.00628

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	CCDC88C: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.91
Dann	Benign	0.93
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: rs61736349; hg19: chr14-91804487; COSMIC: COSV66234130; COSMIC: COSV66234130;