14-91272666-C-A

Variant names:

• chr14-91272666-C-A
• rs10142844
• NM_001080414.4:c.6046G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080414.4(CCDC88C):​c.6046G>T​(p.Gly2016Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC88C NM_001080414.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88C	NM_001080414.4	c.6046G>T	p.Gly2016Trp	missense_variant	Exon 30 of 30	ENST00000389857.11	NP_001073883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11	c.6046G>T	p.Gly2016Trp	missense_variant	Exon 30 of 30	5	NM_001080414.4	ENSP00000374507.6
CCDC88C	ENST00000556726	c.*1880G>T		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000452406.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.86	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.18
Sift	Benign	0.11	T;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	.;D
Vest4		0.50
MutPred		0.30		.;Loss of disorder (P = 0.0028);
MVP		0.64
MPC		0.65
ClinPred		0.97	D
GERP RS		4.1
Varity_R		0.51
gMVP		0.18

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: rs10142844; hg19: chr14-91739010;