rs139544500

Positions:

chr14-91281488-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001080414.4(CCDC88C):c.4668G>A(p.Leu1556=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0074 in 1,613,946 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 53 hom. )

Consequence

CCDC88C
NM_001080414.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.134

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 14-91281488-C-T is Benign according to our data. Variant chr14-91281488-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 447020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91281488-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.134 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00489 (745/152306) while in subpopulation AMR AF= 0.00725 (111/15300). AF 95% confidence interval is 0.00656. There are 3 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC88C	NM_001080414.4 linkuse as main transcript	c.4668G>A	p.Leu1556=	synonymous_variant	27/30	ENST00000389857.11	NP_001073883.2
CCDC88C	XM_011536796.3 linkuse as main transcript	c.4560G>A	p.Leu1520=	synonymous_variant	27/30		XP_011535098.1
CCDC88C	XM_047431418.1 linkuse as main transcript	c.4401G>A	p.Leu1467=	synonymous_variant	24/27		XP_047287374.1
CCDC88C	XM_047431419.1 linkuse as main transcript	c.4668G>A	p.Leu1556=	synonymous_variant	27/28		XP_047287375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88C	ENST00000389857.11 linkuse as main transcript	c.4668G>A	p.Leu1556=	synonymous_variant	27/30	5	NM_001080414.4	ENSP00000374507	P1	Q9P219-1
CCDC88C	ENST00000334448.5 linkuse as main transcript	n.333G>A		non_coding_transcript_exon_variant	2/6	1
CCDC88C	ENST00000556726.5 linkuse as main transcript	c.*502G>A		3_prime_UTR_variant	4/7	5		ENSP00000452406

Frequencies

GnomAD3 genomes

AF:

0.00491

AC:

747

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00710

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00563

AC:

1403

AN:

249274

Hom.:

AF XY:

0.00551

AC XY:

745

AN XY:

135226

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00701

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00181

Gnomad NFE exome

AF:

0.00793

Gnomad OTH exome

AF:

0.00875

GnomAD4 exome

AF:

0.00767

AC:

11205

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

5368

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00729

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00884

Gnomad4 OTH exome

AF:

0.00787

GnomAD4 genome

AF:

0.00489

AC:

745

AN:

152306

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

334

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00725

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00709

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00682

Hom.:

Bravo

AF:

0.00578

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.0101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	CCDC88C: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Oct 03, 2016

- -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.1

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over