Genetic Variant NM_001080414.4:c.6012C>G (chr14-91272700-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is . The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001080414.4(CCDC88C):c.6012C>G(p.Val2004Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V2004V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hydrocephalus, nonsyndromic, autosomal recessive 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
spinocerebellar ataxia type 40
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

CCDC88C links:

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new If you want to explore the variant's impact on the transcript NM_001080414.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=1.88 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080414.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC88C	NM_001080414.4	MANE Select	c.6012C>G	p.Val2004Val	synonymous	Exon 30 of 30	NP_001073883.2	Q9P219-1
CCDC88C	NR_189158.1		n.6289C>G		non_coding_transcript_exon	Exon 31 of 31
CCDC88C	NR_189159.1		n.6584C>G		non_coding_transcript_exon	Exon 31 of 31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.6012C>G	p.Val2004Val	synonymous	Exon 30 of 30	ENSP00000374507.6	Q9P219-1
	CCDC88C	ENST00000556726.5	TSL:5	c.*1846C>G		3_prime_UTR	Exon 7 of 7	ENSP00000452406.1	H0YJX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.90

(source)

DANN

Benign

0.26

PhyloP100

1.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over