dbSNP rs782089419: CCDC22:p.Leu403Leu (chrX-49248305-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014008.5(CCDC22):c.1207C>T(p.Leu403Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,057,513 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., 1 hem., cov: 19)

Exomes 𝑓: 0.000010 ( 0 hom. 5 hem. )

Consequence

CCDC22
NM_014008.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-49248305-C-T is Benign according to our data. Variant chrX-49248305-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 434615.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.07 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC22	NM_014008.5 link	c.1207C>T	p.Leu403Leu	synonymous_variant	Exon 10 of 17	ENST00000376227.4	NP_054727.1	O60826A0A024QZ03
CCDC22	XM_005272599.5 link	c.1204C>T	p.Leu402Leu	synonymous_variant	Exon 10 of 17		XP_005272656.1
CCDC22	XR_430506.4 link	n.1370C>T		non_coding_transcript_exon_variant	Exon 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4 link	c.1207C>T	p.Leu403Leu	synonymous_variant	Exon 10 of 17	1	NM_014008.5	ENSP00000365401.3		O60826

Frequencies

GnomAD3 genomes

AF:

0.0000112

AC:

AN:

88997

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000683

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000245

AC:

AN:

163416

AF XY:

0.0000371

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000103

AC:

AN:

968516

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

314810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22662

American (AMR)

AF:

0.00

AC:

AN:

30961

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14941

East Asian (EAS)

AF:

0.00

AC:

AN:

18459

South Asian (SAS)

AF:

0.000192

AC:

AN:

52104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27385

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2957

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

761479

Other (OTH)

AF:

0.00

AC:

AN:

37568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000112

AC:

AN:

88997

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

21443

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23305

American (AMR)

AF:

0.00

AC:

AN:

7146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2382

East Asian (EAS)

AF:

0.00

AC:

AN:

2352

South Asian (SAS)

AF:

0.000683

AC:

AN:

1465

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

200

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

47177

Other (OTH)

AF:

0.00

AC:

AN:

1180

Age Distribution

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:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 01, 2016

Genetic Services Laboratory, University of Chicago

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

-0.51

CADD

Benign

9.1

(source)

DANN

Benign

0.59

PhyloP100

1.1

Mutation Taster

=100/0

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

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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