NM_014008.5:c.1288G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014008.5(CCDC22):c.1288G>A(p.Ala430Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00765 in 1,207,914 control chromosomes in the GnomAD database, including 24 homozygotes. There are 2,961 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 2 hom., 181 hem., cov: 23)

Exomes 𝑓: 0.0078 ( 22 hom. 2780 hem. )

Consequence

CCDC22
NM_014008.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.63

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008079827).

BP6

Variant X-49248482-G-A is Benign according to our data. Variant chrX-49248482-G-A is described in ClinVar as Benign. ClinVar VariationId is 95548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00782 (8578/1096345) while in subpopulation MID AF = 0.0247 (102/4123). AF 95% confidence interval is 0.0209. There are 22 homozygotes in GnomAdExome4. There are 2780 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC22	NM_014008.5 link	c.1288G>A	p.Ala430Thr	missense_variant	Exon 11 of 17	ENST00000376227.4	NP_054727.1	O60826A0A024QZ03
CCDC22	XM_005272599.5 link	c.1285G>A	p.Ala429Thr	missense_variant	Exon 11 of 17		XP_005272656.1
CCDC22	XR_430506.4 link	n.1451G>A		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4 link	c.1288G>A	p.Ala430Thr	missense_variant	Exon 11 of 17	1	NM_014008.5	ENSP00000365401.3		O60826

Frequencies

GnomAD3 genomes

AF:

0.00595

AC:

663

AN:

111517

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00444

Gnomad ASJ

AF:

0.00833

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.00189

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00818

Gnomad OTH

AF:

0.00598

GnomAD2 exomes

AF:

0.00737

AC:

1320

AN:

179019

AF XY:

0.00665

show subpopulations

Gnomad AFR exome

AF:

0.000469

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.00927

Gnomad OTH exome

AF:

0.00793

GnomAD4 exome

AF:

0.00782

AC:

8578

AN:

1096345

Hom.:

Cov.:

AF XY:

0.00768

AC XY:

2780

AN XY:

362065

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

26379

American (AMR)

AF:

0.00358

AC:

126

AN:

35149

Ashkenazi Jewish (ASJ)

AF:

0.0105

AC:

203

AN:

19363

East Asian (EAS)

AF:

0.00

AC:

AN:

30176

South Asian (SAS)

AF:

0.00404

AC:

218

AN:

53929

European-Finnish (FIN)

AF:

0.0186

AC:

741

AN:

39911

Middle Eastern (MID)

AF:

0.0247

AC:

102

AN:

4123

European-Non Finnish (NFE)

AF:

0.00807

AC:

6793

AN:

841292

Other (OTH)

AF:

0.00797

AC:

367

AN:

46023

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

347

694

1041

1388

1735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.00595

AC:

664

AN:

111569

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

181

AN XY:

33777

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

30759

American (AMR)

AF:

0.00443

AC:

AN:

10609

Ashkenazi Jewish (ASJ)

AF:

0.00833

AC:

AN:

2642

East Asian (EAS)

AF:

0.000284

AC:

AN:

3527

South Asian (SAS)

AF:

0.00189

AC:

AN:

2640

European-Finnish (FIN)

AF:

0.0179

AC:

108

AN:

6038

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00820

AC:

434

AN:

52928

Other (OTH)

AF:

0.00591

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

126

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:

0.00784

Hom.:

338

Bravo

AF:

0.00491

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00588

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00803

AC:

ExAC

AF:

0.00803

AC:

974

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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:1

Aug 12, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ritscher-Schinzel syndrome 2

Benign:1

May 18, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.3

PhyloP100

4.6

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.65

REVEL

Benign

0.18

Sift

Benign

0.15

Sift4G

Benign

0.54

Polyphen

0.99

Vest4

0.10

MVP

0.70

MPC

0.44

ClinPred

0.017

GERP RS

5.2

Varity_R

0.15

gMVP

0.042

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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