Variant 11-60849953-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024098.4(CCDC86):c.902G>A(p.Arg301His) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

CCDC86
NM_024098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

Variant links:

Genes affected

CCDC86 (HGNC:28359): (coiled-coil domain containing 86) Enables RNA binding activity. Located in chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC86 links:

CCDC86-AS1 (HGNC:56314): (CCDC86 antisense RNA 1)

CCDC86-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC86	NM_024098.4 linkuse as main transcript	c.902G>A	p.Arg301His	missense_variant	3/4	ENST00000227520.10	NP_077003.1
CCDC86-AS1	NR_182293.1 linkuse as main transcript	n.316+813C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC86	ENST00000227520.10 linkuse as main transcript	c.902G>A	p.Arg301His	missense_variant	3/4	1	NM_024098.4	ENSP00000227520	P1	Q9H6F5-1
CCDC86-AS1	ENST00000538705.1 linkuse as main transcript	n.316+813C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000917

AC:

AN:

250876

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000589

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1461746

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000568

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000105

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000282

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Aug 16, 2021

The c.902G>A (p.R301H) alteration is located in exon 3 (coding exon 3) of the CCDC86 gene. This alteration results from a G to A substitution at nucleotide position 902, causing the arginine (R) at amino acid position 301 to be replaced by a histidine (H). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.63

D;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.61

D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;.

Vest4

0.57

MVP

0.92

MPC

1.2

ClinPred

0.91

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.38

gMVP

0.13

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