rs191605685

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014008.5(CCDC22):c.536-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,197,339 control chromosomes in the GnomAD database, including 13 homozygotes. There are 1,853 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 0 hom., 106 hem., cov: 23)

Exomes 𝑓: 0.0048 ( 13 hom. 1747 hem. )

Consequence

CCDC22
NM_014008.5 splice_region, intron

Scores

Splicing: ADA: 0.00002202

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.159

Publications

0 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant X-49243277-C-T is Benign according to our data. Variant chrX-49243277-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 106 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC22	NM_014008.5 link	c.536-7C>T	splice_region_variant, intron_variant	Intron 5 of 16	ENST00000376227.4	NP_054727.1	O60826A0A024QZ03
CCDC22	XM_005272599.5 link	c.533-7C>T	splice_region_variant, intron_variant	Intron 5 of 16		XP_005272656.1
CCDC22	XR_430506.4 link	n.703-7C>T	splice_region_variant, intron_variant	Intron 5 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC22	ENST00000376227.4 link	c.536-7C>T	splice_region_variant, intron_variant	Intron 5 of 16	1	NM_014008.5	ENSP00000365401.3	O60826
CCDC22	ENST00000490300.1 link	n.679-7C>T	splice_region_variant, intron_variant	Intron 4 of 4	3
CCDC22	ENST00000496651.5 link	n.627-7C>T	splice_region_variant, intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.00332

AC:

374

AN:

112639

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000904

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00214

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00366

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00541

Gnomad OTH

AF:

0.00265

GnomAD2 exomes

AF:

0.00363

AC:

584

AN:

160921

AF XY:

0.00413

show subpopulations

Gnomad AFR exome

AF:

0.000665

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.000630

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00248

Gnomad NFE exome

AF:

0.00600

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00479

AC:

5192

AN:

1084645

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

1747

AN XY:

351855

show subpopulations

African (AFR)

AF:

0.000305

AC:

AN:

26239

American (AMR)

AF:

0.00123

AC:

AN:

34139

Ashkenazi Jewish (ASJ)

AF:

0.000694

AC:

AN:

18725

East Asian (EAS)

AF:

0.00

AC:

AN:

29934

South Asian (SAS)

AF:

0.00526

AC:

274

AN:

52048

European-Finnish (FIN)

AF:

0.00258

AC:

103

AN:

39888

Middle Eastern (MID)

AF:

0.00859

AC:

AN:

4074

European-Non Finnish (NFE)

AF:

0.00545

AC:

4543

AN:

834116

Other (OTH)

AF:

0.00383

AC:

174

AN:

45482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

188

375

563

750

938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.00333

AC:

375

AN:

112694

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

106

AN XY:

34862

show subpopulations

African (AFR)

AF:

0.000902

AC:

AN:

31057

American (AMR)

AF:

0.00213

AC:

AN:

10778

Ashkenazi Jewish (ASJ)

AF:

0.00113

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3569

South Asian (SAS)

AF:

0.00404

AC:

AN:

2726

European-Finnish (FIN)

AF:

0.00255

AC:

AN:

6278

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00541

AC:

288

AN:

53200

Other (OTH)

AF:

0.00261

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00465

Hom.:

Bravo

AF:

0.00260

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Sep 07, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 14, 2019

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual disability

Benign:1

Oct 09, 2019

Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ritscher-Schinzel syndrome 2

Benign:1

Jan 17, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.48

(source)

DANN

Benign

0.72

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over