Variant 14-91272677-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001080414.4(CCDC88C):c.6035C>A(p.Pro2012Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.42

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36488497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 link	c.6035C>A	p.Pro2012Gln	missense_variant	Exon 30 of 30	ENST00000389857.11	NP_001073883.2	Q9P219-1B4DZB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 link	c.6035C>A	p.Pro2012Gln	missense_variant	Exon 30 of 30	5	NM_001080414.4	ENSP00000374507.6		Q9P219-1
CCDC88C	ENST00000556726 link	c.*1869C>A		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000452406.1		H0YJX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000825

AC:

AN:

242324

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132788

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459236

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725960

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

ExAC

AF:

0.00000833

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

T;D

M_CAP

Benign

0.067

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Pathogenic

2.9

.;M

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.7

.;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

.;D

Vest4

0.68

MutPred

0.17

.;Gain of solvent accessibility (P = 0.0202);

MVP

0.59

MPC

0.57

ClinPred

0.95

GERP RS

4.1

Varity_R

0.23

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over