rs183742506

chr14-91339321-G-Achr14-91339321-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001080414.4(CCDC88C):c.766C>T(p.Leu256=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00351 in 1,613,598 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L256L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (13 hom.)
• Consequence: CCDC88C NM_001080414.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.21

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 14-91339321-G-A is Benign according to our data. Variant chr14-91339321-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0027 (412/152370) while in subpopulation NFE AF= 0.00466 (317/68038). AF 95% confidence interval is 0.00424. There are 1 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88C	NM_001080414.4	c.766C>T	p.Leu256=	synonymous_variant	8/30	ENST00000389857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88C	ENST00000389857.11	c.766C>T	p.Leu256=	synonymous_variant	8/30	5	NM_001080414.4	P1
CCDC88C	ENST00000554872.5	n.706C>T		non_coding_transcript_exon_variant	7/7	4

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 412 AN: 152252 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00466

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00246 AC: 609 AN: 247742 Hom.: 3 AF XY: 0.00241 AC XY: 325 AN XY: 134662

Gnomad AFR exome AF: 0.000584

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.00280

Gnomad NFE exome AF: 0.00422

Gnomad OTH exome AF: 0.00299

GnomAD4 exome AF: 0.00359 AC: 5253 AN: 1461228 Hom.: 13 Cov.: 31 AF XY: 0.00349 AC XY: 2535 AN XY: 726894

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00281

Gnomad4 NFE exome AF: 0.00433

Gnomad4 OTH exome AF: 0.00288

GnomAD4 genome AF: 0.00270 AC: 412 AN: 152370 Hom.: 1 Cov.: 33 AF XY: 0.00251 AC XY: 187 AN XY: 74502

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00466

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00278 Hom.: 0

Bravo AF: 0.00271

EpiCase AF: 0.00453

EpiControl AF: 0.00380

ClinVar

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

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jun 22, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	11
Dann	Benign	0.77

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: rs183742506; hg19: chr14-91805665;