dbSNP rs61736349: CCDC88C:p.Asp304Asp (chr14-91338143-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001080414.4(CCDC88C):c.912C>T(p.Asp304Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,613,808 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 44 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.510

Publications

3 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 14-91338143-G-A is Benign according to our data. Variant chr14-91338143-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.51 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00431 (656/152328) while in subpopulation NFE AF = 0.00725 (493/68034). AF 95% confidence interval is 0.00672. There are 3 homozygotes in GnomAd4. There are 279 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR 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.912C>T	p.Asp304Asp	synonymous	Exon 10 of 30	NP_001073883.2	Q9P219-1
CCDC88C	NR_189158.1		n.1042C>T		non_coding_transcript_exon	Exon 10 of 31
CCDC88C	NR_189159.1		n.1042C>T		non_coding_transcript_exon	Exon 10 of 31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.912C>T	p.Asp304Asp	synonymous	Exon 10 of 30	ENSP00000374507.6	Q9P219-1
	CCDC88C	ENST00000554051.1	TSL:3	n.389C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

656

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00420

AC:

1045

AN:

248686

AF XY:

0.00423

show subpopulations

Gnomad AFR exome

AF:

0.00188

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00289

Gnomad EAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.00372

Gnomad NFE exome

AF:

0.00714

Gnomad OTH exome

AF:

0.00348

GnomAD4 exome

AF:

0.00627

AC:

9168

AN:

1461480

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

4440

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

33480

American (AMR)

AF:

0.00134

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00329

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.000858

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00417

AC:

222

AN:

53252

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00754

AC:

8382

AN:

1111810

Other (OTH)

AF:

0.00495

AC:

299

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

502

1004

1507

2009

2511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.00431

AC:

656

AN:

152328

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41568

American (AMR)

AF:

0.00203

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00187

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00725

AC:

493

AN:

68034

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00563

Hom.:

Bravo

AF:

0.00400

EpiCase

AF:

0.00573

EpiControl

AF:

0.00628

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.91

(source)

DANN

Benign

0.93

PhyloP100

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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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