Variant rs548084281 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012506.5(CCDC66):c.-29A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000094 in 1,542,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

CCDC66
NM_001012506.5 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.007349

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0980

Variant links:

Genes affected

CCDC66 (HGNC:27709): (coiled-coil domain containing 66) Enables microtubule binding activity. Involved in cilium assembly; microtubule bundle formation; and regulation of protein localization to cilium. Located in several cellular components, including Flemming body; microtubule cytoskeleton; and photoreceptor inner segment. [provided by Alliance of Genome Resources, Apr 2022]

CCDC66 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01966986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC66	NM_001141947.3 link	c.74A>G	p.Tyr25Cys	missense_variant, splice_region_variant	Exon 2 of 18	ENST00000394672.8	NP_001135419.1	A2RUB6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC66	ENST00000394672.8 link	c.74A>G	p.Tyr25Cys	missense_variant, splice_region_variant	Exon 2 of 18	1	NM_001141947.3	ENSP00000378167.3		A2RUB6-1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000902

AC:

AN:

155290

Hom.:

AF XY:

0.0000609

AC XY:

AN XY:

82160

show subpopulations

Gnomad AFR exome

AF:

0.00176

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000597

AC:

AN:

1390522

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

686218

show subpopulations

Gnomad4 AFR exome

AF:

0.000828

Gnomad4 AMR exome

AF:

0.0000283

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000476

Gnomad4 OTH exome

AF:

0.0000347

GnomAD4 genome

AF:

0.000407

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000839

Hom.:

Bravo

AF:

0.000393

ExAC

AF:

0.000122

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.74A>G (p.Y25C) alteration is located in exon 2 (coding exon 2) of the CCDC66 gene. This alteration results from a A to G substitution at nucleotide position 74, causing the tyrosine (Y) at amino acid position 25 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.035

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.020

T;T

MetaSVM

Pathogenic

0.87

MutationAssessor

Benign

1.4

.;L

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.4

N;D

REVEL

Uncertain

0.40

Sift

Benign

0.11

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.023

.;B

Vest4

0.27

MVP

0.59

MPC

0.11

ClinPred

0.081

GERP RS

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0073

dbscSNV1_RF

Benign

0.16

SpliceAI score (max)

0.030

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