rs112211533

Positions:

• chr14-91300084-G-A
• chr14-91300084-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080414.4(CCDC88C):​c.3636-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,604,306 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (57 hom.)
• Consequence: CCDC88C NM_001080414.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00600

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 14-91300084-G-A is Benign according to our data. Variant chr14-91300084-G-A is described in ClinVar as [Benign]. Clinvar id is 158109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88C	NM_001080414.4	c.3636-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389857.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88C	ENST00000389857.11	c.3636-14C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001080414.4	P1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2364 AN: 152258 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00536

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00381 AC: 876 AN: 230088 Hom.: 20 AF XY: 0.00284 AC XY: 355 AN XY: 125160

Gnomad AFR exome AF: 0.0575

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000142

Gnomad FIN exome AF: 0.000104

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00158 AC: 2299 AN: 1451930 Hom.: 57 Cov.: 31 AF XY: 0.00135 AC XY: 976 AN XY: 721404

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000142

Gnomad4 FIN exome AF: 0.000117

Gnomad4 NFE exome AF: 0.0000839

Gnomad4 OTH exome AF: 0.00357

GnomAD4 genome AF: 0.0157 AC: 2393 AN: 152376 Hom.: 62 Cov.: 33 AF XY: 0.0156 AC XY: 1159 AN XY: 74514

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00842 Hom.: 4

Bravo AF: 0.0177

Asia WGS AF: 0.00260 AC: 9 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 11, 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	-0.93
CADD	Benign	0.29
DANN	Benign	0.40

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: rs112211533; hg19: chr14-91766428;