dbSNP rs782159081: CCDC22:p.Asp99Glu (chrX-49242084-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014008.5(CCDC22):c.297C>G(p.Asp99Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,208,394 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

CCDC22
NM_014008.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.0390

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: 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0729081).

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.297C>G	p.Asp99Glu	missense	Exon 3 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.297C>G	p.Asp99Glu	missense	Exon 3 of 17	ENSP00000365401.3	O60826
CCDC22	ENST00000960401.1		c.297C>G	p.Asp99Glu	missense	Exon 3 of 17	ENSP00000630460.1
CCDC22	ENST00000904959.1		c.315C>G	p.Asp105Glu	missense	Exon 3 of 17	ENSP00000575018.1

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

110537

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000990

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

GnomAD2 exomes

AF:

0.00000548

AC:

AN:

182428

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000765

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000364

AC:

AN:

1097857

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363223

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

35188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.00

AC:

AN:

30200

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841883

Other (OTH)

AF:

0.0000434

AC:

AN:

46082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000271

AC:

AN:

110537

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32761

show subpopulations

African (AFR)

AF:

0.0000990

AC:

AN:

30300

American (AMR)

AF:

0.00

AC:

AN:

10441

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3509

South Asian (SAS)

AF:

0.00

AC:

AN:

2485

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52746

Other (OTH)

AF:

0.00

AC:

AN:

1474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.18

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.70

M_CAP

Benign

0.0030

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.039

PrimateAI

Uncertain

0.58

PROVEAN

Benign

1.1

REVEL

Benign

0.055

Sift

Benign

0.95

Sift4G

Benign

0.75

Polyphen

0.042

Vest4

0.25

MutPred

0.42

Gain of disorder (P = 0.1982)

MVP

0.53

MPC

0.88

ClinPred

0.074

GERP RS

-0.20

Varity_R

0.064

gMVP

0.30

Mutation Taster

=99/1

polymorphism

(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

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