Variant 11-96371059-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024725.4(CCDC82):c.1163G>A(p.Arg388His) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,606,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CCDC82
NM_024725.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

Variant links:

Genes affected

CCDC82 (HGNC:26282): (coiled-coil domain containing 82) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCDC82 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
CCDC82	NM_024725.4 linkuse as main transcript	c.1163G>A	p.Arg388His	missense_variant	7/10	ENST00000646818.2	NP_079001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC82	ENST00000646818.2 linkuse as main transcript	c.1163G>A	p.Arg388His	missense_variant	7/10		NM_024725.4	ENSP00000496393		Q8N4S0-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246198

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133112

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000963

AC:

AN:

1454104

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

723066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000902

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

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

Oct 10, 2023

The c.1163G>A (p.R388H) alteration is located in exon 7 (coding exon 4) of the CCDC82 gene. This alteration results from a G to A substitution at nucleotide position 1163, causing the arginine (R) at amino acid position 388 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;T;T;T;T;T;T;.;.;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

.;.;.;.;.;.;.;D;D;D;D

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.55

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.1

M;M;M;M;M;M;M;.;.;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.8

D;.;.;.;.;.;.;.;.;.;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0080

D;.;.;.;.;.;.;.;.;.;D

Sift4G

Pathogenic

0.0

D;.;.;.;.;.;.;.;.;.;D

Polyphen

1.0

D;D;D;D;D;D;D;.;.;.;D

Vest4

0.47

MutPred

0.57

Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);Gain of catalytic residue at R388 (P = 0.0075);

MVP

0.59

MPC

0.42

ClinPred

0.93

GERP RS

4.6

Varity_R

0.37

gMVP

0.65

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