dbSNP rs2294021: CCDC22:c.1540-18T>C (chrX-49249149-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_014008.5(CCDC22):c.1540-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 10557 hom., 16860 hem., cov: 24)

Exomes 𝑓: 0.57 ( 120278 hom. 201744 hem. )

Failed GnomAD Quality Control

Consequence

CCDC22
NM_014008.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.97

Publications

47 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: ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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

new If you want to explore the variant's impact on the transcript NM_014008.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-49249149-T-C is Benign according to our data. Variant chrX-49249149-T-C is described in ClinVar as Benign. ClinVar VariationId is 284920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1540-18T>C		intron	N/A	NP_054727.1	O60826

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCDC22	ENST00000376227.4	TSL:1 MANE Select	c.1540-18T>C	intron	N/A	ENSP00000365401.3	O60826
CCDC22	ENST00000960401.1		c.1564-18T>C	intron	N/A	ENSP00000630460.1
CCDC22	ENST00000904959.1		c.1558-18T>C	intron	N/A	ENSP00000575018.1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

56780

AN:

111703

Hom.:

10555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.506

GnomAD2 exomes

AF:

0.522

AC:

91508

AN:

175177

AF XY:

0.535

show subpopulations

Gnomad AFR exome

AF:

0.411

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.578

Gnomad EAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.532

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.572

AC:

618923

AN:

1082239

Hom.:

120278

Cov.:

AF XY:

0.577

AC XY:

201744

AN XY:

349721

show subpopulations

African (AFR)

AF:

0.407

AC:

10632

AN:

26118

American (AMR)

AF:

0.413

AC:

14377

AN:

34852

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

11259

AN:

19251

East Asian (EAS)

AF:

0.396

AC:

11912

AN:

30101

South Asian (SAS)

AF:

0.581

AC:

31114

AN:

53529

European-Finnish (FIN)

AF:

0.510

AC:

20433

AN:

40072

Middle Eastern (MID)

AF:

0.572

AC:

2349

AN:

4105

European-Non Finnish (NFE)

AF:

0.593

AC:

491512

AN:

828677

Other (OTH)

AF:

0.556

AC:

25335

AN:

45534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10002

20004

30006

40008

50010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15234

30468

45702

60936

76170

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.508

AC:

56814

AN:

111755

Hom.:

10557

Cov.:

AF XY:

0.496

AC XY:

16860

AN XY:

33981

show subpopulations

African (AFR)

AF:

0.408

AC:

12581

AN:

30803

American (AMR)

AF:

0.441

AC:

4719

AN:

10689

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

1538

AN:

2646

East Asian (EAS)

AF:

0.384

AC:

1344

AN:

3501

South Asian (SAS)

AF:

0.574

AC:

1559

AN:

2718

European-Finnish (FIN)

AF:

0.491

AC:

2967

AN:

6046

Middle Eastern (MID)

AF:

0.576

AC:

125

AN:

217

European-Non Finnish (NFE)

AF:

0.583

AC:

30846

AN:

52923

Other (OTH)

AF:

0.510

AC:

786

AN:

1541

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1027

2053

3080

4106

5133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.547

Hom.:

56000

Bravo

AF:

0.498

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Ritscher-Schinzel syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.26

(source)

DANN

Benign

0.76

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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