Variant 11-86400776-G-A 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_001156474.2(CCDC81):c.856G>A(p.Gly286Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CCDC81
NM_001156474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.315

Variant links:

Genes affected

CCDC81 (HGNC:26281): (coiled-coil domain containing 81) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CCDC81 links:

CCDC81 (HGNC:):

CCDC81 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=0.023208141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC81	NM_001156474.2 linkuse as main transcript	c.856G>A	p.Gly286Ser	missense_variant	7/15	ENST00000445632.7	NP_001149946.1	Q6ZN84-1
CCDC81	NM_021827.5 linkuse as main transcript	c.586G>A	p.Gly196Ser	missense_variant	6/14		NP_068599.3	Q6ZN84-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC81	ENST00000445632.7 linkuse as main transcript	c.856G>A	p.Gly286Ser	missense_variant	7/15	1	NM_001156474.2	ENSP00000415528.2		Q6ZN84-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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:

0.0000199

AC:

AN:

251050

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

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:

0.00000343

AC:

AN:

1459304

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725562

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.856G>A (p.G286S) alteration is located in exon 7 (coding exon 7) of the CCDC81 gene. This alteration results from a G to A substitution at nucleotide position 856, causing the glycine (G) at amino acid position 286 to be replaced by a serine (S). 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

0.074

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.2

DANN

Benign

0.91

DEOGEN2

Benign

0.00069

.;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.5

.;L;.

MutationTaster

Benign

0.63

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.082

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.99

D;B;B

Vest4

0.076

MutPred

0.27

.;Gain of glycosylation at G286 (P = 0.0113);.;

MVP

0.030

MPC

0.15

ClinPred

0.043

GERP RS

4.4

Varity_R

0.067

gMVP

0.21

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

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