NM_014008.5:c.51-25C>T

Variant names:

• chrX-49237061-C-T
• rs2294016
• NM_014008.5:c.51-25C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014008.5(CCDC22):​c.51-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 111,579 control chromosomes in the GnomAD database, including 9,550 homozygotes. There are 14,085 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.43 (9550 hom., 14085 hem., cov: 24)
  • Exomes 𝑓: 0.57 (126793 hom. 200355 hem.)
  • Failed GnomAD Quality Control
• Consequence: CCDC22 NM_014008.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 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: 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

ACMG classification

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

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

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.51-25C>T		intron	N/A	NP_054727.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC22	ENST00000376227.4	TSL:1 MANE Select	c.51-25C>T		intron	N/A	ENSP00000365401.3
	CCDC22	ENST00000960401.1		c.51-25C>T		intron	N/A	ENSP00000630460.1
	CCDC22	ENST00000904959.1		c.51-25C>T		intron	N/A	ENSP00000575018.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 47752 AN: 111523 Hom.: 9557 Cov.: 24

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.475

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.574 AC: 619307 AN: 1078301 Hom.: 126793 Cov.: 27 AF XY: 0.576 AC XY: 200355 AN XY: 347585

African (AFR) AF: 0.0826 AC: 2150 AN: 26025

American (AMR) AF: 0.302 AC: 10439 AN: 34535

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 13399 AN: 19028

East Asian (EAS) AF: 0.166 AC: 4954 AN: 29761

South Asian (SAS) AF: 0.429 AC: 22692 AN: 52855

European-Finnish (FIN) AF: 0.552 AC: 22133 AN: 40125

Middle Eastern (MID) AF: 0.622 AC: 2536 AN: 4075

European-Non Finnish (NFE) AF: 0.625 AC: 516554 AN: 826678

Other (OTH) AF: 0.541 AC: 24450 AN: 45219

GnomAD4 genome AF: 0.428 AC: 47739 AN: 111579 Hom.: 9550 Cov.: 24 AF XY: 0.417 AC XY: 14085 AN XY: 33805

African (AFR) AF: 0.0941 AC: 2908 AN: 30902

American (AMR) AF: 0.376 AC: 3973 AN: 10574

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 1867 AN: 2633

East Asian (EAS) AF: 0.153 AC: 540 AN: 3526

South Asian (SAS) AF: 0.393 AC: 1064 AN: 2708

European-Finnish (FIN) AF: 0.540 AC: 3197 AN: 5915

Middle Eastern (MID) AF: 0.647 AC: 139 AN: 215

European-Non Finnish (NFE) AF: 0.622 AC: 32922 AN: 52923

Other (OTH) AF: 0.473 AC: 718 AN: 1518

Alfa AF: 0.536 Hom.: 25565

Bravo AF: 0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.077
PhyloP100		-1.1
BranchPoint Hunter		3.0

Splicing

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

Other links and lift over

dbSNP: rs2294016; hg19: chrX-49093528;