chrX-49237077-C-T

Variant names:

• chrX-49237077-C-T
• rs1443511548
• NM_014008.5:c.51-9C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_014008.5(CCDC22):​c.51-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 112,625 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: CCDC22 NM_014008.5 intron
• Scores: Splicing: ADA: 0.00001216
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.230
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant X-49237077-C-T is Benign according to our data. Variant chrX-49237077-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3052729.Status of the report is no_assertion_criteria_provided, 0 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.51-9C>T		intron	N/A	NP_054727.1	O60826

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC22	ENST00000376227.4	TSL:1 MANE Select	c.51-9C>T		intron	N/A	ENSP00000365401.3	O60826
	CCDC22	ENST00000960401.1		c.51-9C>T		intron	N/A	ENSP00000630460.1
	CCDC22	ENST00000904959.1		c.51-9C>T		intron	N/A	ENSP00000575018.1

Frequencies

GnomAD3 genomes AF: 0.00000888 AC: 1 AN: 112625 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000323

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

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000888 AC: 1 AN: 112625 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34765

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000323 AC: 1 AN: 30982

American (AMR) AF: 0.00 AC: 0 AN: 10699

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3592

South Asian (SAS) AF: 0.00 AC: 0 AN: 2773

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6195

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53295

Other (OTH) AF: 0.00 AC: 0 AN: 1510

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CCDC22-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		-0.23

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.062
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1443511548; hg19: chrX-49093544;