14-91272685-C-T

Position:

• chr14-91272685-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001080414.4(CCDC88C):​c.6027G>A​(p.Pro2009=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,611,708 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (6 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.45

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-91272685-C-T is Benign according to our data. Variant chr14-91272685-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 708836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91272685-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-3.45 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4	c.6027G>A	p.Pro2009=	synonymous_variant	30/30	ENST00000389857.11	NP_001073883.2
CCDC88C	XM_011536796.3	c.5919G>A	p.Pro1973=	synonymous_variant	30/30		XP_011535098.1
CCDC88C	XM_047431418.1	c.5760G>A	p.Pro1920=	synonymous_variant	27/27		XP_047287374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11	c.6027G>A	p.Pro2009=	synonymous_variant	30/30	5	NM_001080414.4	ENSP00000374507	P1
CCDC88C	ENST00000556726.5	c.*1861G>A		3_prime_UTR_variant	7/7	5		ENSP00000452406

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 258 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00194 AC: 471 AN: 242678 Hom.: 1 AF XY: 0.00222 AC XY: 295 AN XY: 132942

Gnomad AFR exome AF: 0.000549

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.000202

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00357

Gnomad FIN exome AF: 0.00149

Gnomad NFE exome AF: 0.00249

Gnomad OTH exome AF: 0.00235

GnomAD4 exome AF: 0.00238 AC: 3469 AN: 1459376 Hom.: 6 Cov.: 29 AF XY: 0.00248 AC XY: 1800 AN XY: 726036

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00339

Gnomad4 FIN exome AF: 0.00179

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00169 AC: 258 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.00177 AC XY: 132 AN XY: 74484

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00196

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00207

EpiControl AF: 0.00261

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	CCDC88C: BP4, BP7 -

Hydrocephalus, nonsyndromic, autosomal recessive 1;C4518336:Spinocerebellar ataxia type 40 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.071
DANN	Benign	0.42

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: rs200979954; hg19: chr14-91739029;