Variant rs183877705 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014008.5(CCDC22):c.926C>A(p.Ala309Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,196,386 control chromosomes in the GnomAD database, including 3 homozygotes. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 8 hem., cov: 25)

Exomes 𝑓: 0.000078 ( 3 hom. 29 hem. )

Consequence

CCDC22
NM_014008.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.534

Variant links:

Genes affected

CCDC22 (HGNC:28909): (coiled-coil domain containing 22) This gene encodes a protein containing a coiled-coil domain. The encoded protein functions in the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) by interacting with COMMD (copper metabolism Murr1 domain-containing) proteins. The mouse orthologous protein has been shown to bind copines, which are calcium-dependent, membrane-binding proteins that may function in calcium signaling. This human gene has been identified as a novel candidate gene for syndromic X-linked intellectual disability. [provided by RefSeq, Aug 2013]

CCDC22 links:

CCDC22 (HGNC:):

CCDC22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009794652).

BP6

Variant X-49247512-C-A is Benign according to our data. Variant chrX-49247512-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 434613.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC22	NM_014008.5 linkuse as main transcript	c.926C>A	p.Ala309Asp	missense_variant	8/17	ENST00000376227.4	NP_054727.1	O60826A0A024QZ03
CCDC22	XM_005272599.5 linkuse as main transcript	c.923C>A	p.Ala308Asp	missense_variant	8/17		XP_005272656.1
CCDC22	XR_430506.4 linkuse as main transcript	n.1093C>A		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4 linkuse as main transcript	c.926C>A	p.Ala309Asp	missense_variant	8/17	1	NM_014008.5	ENSP00000365401.3		O60826

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

112570

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34718

show subpopulations

Gnomad AFR

AF:

0.000548

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000783

AC:

AN:

153164

Hom.:

AF XY:

0.00

AC XY:

AN XY:

48526

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000394

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:

0.0000775

AC:

AN:

1083764

Hom.:

Cov.:

AF XY:

0.0000819

AC XY:

AN XY:

354174

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.0000295

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.000195

AC:

AN:

112622

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

34780

show subpopulations

Gnomad4 AFR

AF:

0.000708

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000755

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 26, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.38

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

REVEL

Benign

0.035

Sift

Benign

0.038

Sift4G

Benign

0.086

Polyphen

0.17

Vest4

0.31

MVP

0.28

MPC

0.22

ClinPred

0.017

GERP RS

2.8

Varity_R

0.36

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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