14-91417623-G-T

Position:

• chr14-91417623-G-T

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.60+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,580,304 control chromosomes in the GnomAD database, including 140,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12126 hom., cov: 31)
  • Exomes 𝑓: 0.42 (128516 hom.)
• Consequence: CCDC88C NM_001080414.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003065
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.126

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]

CCDC88C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 14-91417623-G-T is Benign according to our data. Variant chr14-91417623-G-T is described in ClinVar as [Benign]. Clinvar id is 158120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91417623-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4	c.60+8C>A		splice_region_variant, intron_variant		ENST00000389857.11	NP_001073883.2
CCDC88C	XM_047431419.1	c.60+8C>A		splice_region_variant, intron_variant
CCDC88C	XM_005267691.6	c.60+8C>A		splice_region_variant, intron_variant
CCDC88C	XM_011536796.3	c.-293C>A		upstream_gene_variant			XP_011535098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11	c.60+8C>A		splice_region_variant, intron_variant		5	NM_001080414.4	ENSP00000374507.6
CCDC88C	ENST00000553403.1	c.60+8C>A		splice_region_variant, intron_variant		1		ENSP00000451392.1
CCDC88C	ENST00000554165.1	n.48+8C>A		splice_region_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58836 AN: 151608 Hom.: 12125 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.384

GnomAD3 exomes AF: 0.415 AC: 84912 AN: 204568 Hom.: 18060 AF XY: 0.419 AC XY: 47651 AN XY: 113842

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.421

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.430

Gnomad FIN exome AF: 0.612

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.420 AC: 600647 AN: 1428588 Hom.: 128516 Cov.: 31 AF XY: 0.422 AC XY: 299283 AN XY: 709930

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.421

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.388 AC: 58848 AN: 151716 Hom.: 12126 Cov.: 31 AF XY: 0.399 AC XY: 29578 AN XY: 74146

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.378

Alfa AF: 0.380 Hom.: 3471

Bravo AF: 0.362

Asia WGS AF: 0.383 AC: 1326 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 08, 2013

- -

Spinocerebellar ataxia type 40 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Hydrocephalus, nonsyndromic, autosomal recessive 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs3742654; hg19: chr14-91883967; COSMIC: COSV66232184; COSMIC: COSV66232184;