14-91272685-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001080414.4(CCDC88C):c.6027G>A(p.Pro2009Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,611,708 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.45

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
spinocerebellar ataxia type 40
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

CCDC88C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 14-91272685-C-T is Benign according to our data. Variant chr14-91272685-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 708836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.45 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR,AD gene

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.6027G>A	p.Pro2009Pro	synonymous	Exon 30 of 30	NP_001073883.2	Q9P219-1
CCDC88C	NR_189158.1		n.6304G>A		non_coding_transcript_exon	Exon 31 of 31
CCDC88C	NR_189159.1		n.6599G>A		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.6027G>A	p.Pro2009Pro	synonymous	Exon 30 of 30	ENSP00000374507.6	Q9P219-1
	CCDC88C	ENST00000556726.5	TSL:5	c.*1861G>A		3_prime_UTR	Exon 7 of 7	ENSP00000452406.1	H0YJX5

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

258

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00194

AC:

471

AN:

242678

AF XY:

0.00222

show subpopulations

Gnomad AFR exome

AF:

0.000549

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.000202

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.00249

Gnomad OTH exome

AF:

0.00235

GnomAD4 exome

AF:

0.00238

AC:

3469

AN:

1459376

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

1800

AN XY:

726036

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33472

American (AMR)

AF:

0.00132

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00339

AC:

292

AN:

86206

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

51406

Middle Eastern (MID)

AF:

0.000714

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.00260

AC:

2895

AN:

1111834

Other (OTH)

AF:

0.00176

AC:

106

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

213

425

638

850

1063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00169

AC:

258

AN:

152332

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41578

American (AMR)

AF:

0.00268

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00251

AC:

171

AN:

68034

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00174

Hom.:

Bravo

AF:

0.00196

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00261

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Hydrocephalus, nonsyndromic, autosomal recessive 1;C4518336:Spinocerebellar ataxia type 40 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.071

(source)

DANN

Benign

0.42

PhyloP100

-3.5

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over