rs143790434

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_014008.5(CCDC22):c.1150C>T(p.Arg384Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,203,066 control chromosomes in the GnomAD database, including 4 homozygotes. There are 1,646 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R384H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., 99 hem., cov: 22)

Exomes 𝑓: 0.0044 ( 4 hom. 1547 hem. )

Consequence

CCDC22
NM_014008.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.316

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

Ritscher-Schinzel syndrome 2
Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
Ritscher-Schinzel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

CCDC22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008935094).

BP6

Variant X-49248248-C-T is Benign according to our data. Variant chrX-49248248-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210615.

BS2

High Hemizygotes in GnomAd4 at 99 XL,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014008.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC22	NM_014008.5	MANE Select	c.1150C>T	p.Arg384Cys	missense	Exon 10 of 17	NP_054727.1	O60826

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC22	ENST00000376227.4	TSL:1 MANE Select	c.1150C>T	p.Arg384Cys	missense	Exon 10 of 17	ENSP00000365401.3	O60826
CCDC22	ENST00000960401.1		c.1174C>T	p.Arg392Cys	missense	Exon 10 of 17	ENSP00000630460.1
CCDC22	ENST00000904959.1		c.1168C>T	p.Arg390Cys	missense	Exon 10 of 17	ENSP00000575018.1

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

398

AN:

109530

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.0120

Gnomad AMR

AF:

0.00587

Gnomad ASJ

AF:

0.000381

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.00542

Gnomad OTH

AF:

0.00342

GnomAD2 exomes

AF:

0.00296

AC:

516

AN:

174156

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.000824

Gnomad EAS exome

AF:

0.0000735

Gnomad FIN exome

AF:

0.00124

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.00390

GnomAD4 exome

AF:

0.00437

AC:

4782

AN:

1093489

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

1547

AN XY:

361015

show subpopulations

African (AFR)

AF:

0.000455

AC:

AN:

26371

American (AMR)

AF:

0.00339

AC:

119

AN:

35155

Ashkenazi Jewish (ASJ)

AF:

0.000981

AC:

AN:

19363

East Asian (EAS)

AF:

0.0000663

AC:

AN:

30176

South Asian (SAS)

AF:

0.000778

AC:

AN:

54010

European-Finnish (FIN)

AF:

0.00139

AC:

AN:

36714

Middle Eastern (MID)

AF:

0.00231

AC:

AN:

3900

European-Non Finnish (NFE)

AF:

0.00515

AC:

4338

AN:

841801

Other (OTH)

AF:

0.00413

AC:

190

AN:

45999

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

242

484

726

968

1210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00361

AC:

396

AN:

109577

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

AN XY:

31965

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

30121

American (AMR)

AF:

0.00587

AC:

AN:

10397

Ashkenazi Jewish (ASJ)

AF:

0.000381

AC:

AN:

2628

East Asian (EAS)

AF:

0.00

AC:

AN:

3415

South Asian (SAS)

AF:

0.00

AC:

AN:

2531

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

5751

Middle Eastern (MID)

AF:

0.00930

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00538

AC:

282

AN:

52372

Other (OTH)

AF:

0.00338

AC:

AN:

1478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00449

Hom.:

Bravo

AF:

0.00354

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00242

AC:

ESP6500AA

AF:

0.00157

AC:

ESP6500EA

AF:

0.00461

AC:

ExAC

AF:

0.00307

AC:

372

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

CCDC22-related disorder (1)

Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.66

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0089

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.4

PhyloP100

0.32

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.12

MVP

0.38

MPC

0.60

ClinPred

0.055

GERP RS

4.1

Varity_R

0.42

gMVP

0.25

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over