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

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014008.5(CCDC22):​c.51-25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=-0.9).

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>A		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>A		intron	N/A	ENSP00000365401.3
	CCDC22	ENST00000960401.1		c.51-25C>A		intron	N/A	ENSP00000630460.1
	CCDC22	ENST00000904959.1		c.51-25C>A		intron	N/A	ENSP00000575018.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1078736 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 347764

African (AFR) AF: 0.00 AC: 0 AN: 26033

American (AMR) AF: 0.00 AC: 0 AN: 34566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19034

East Asian (EAS) AF: 0.00 AC: 0 AN: 29771

South Asian (SAS) AF: 0.00 AC: 0 AN: 52864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40145

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4075

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 827013

Other (OTH) AF: 0.00 AC: 0 AN: 45235

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.070
PhyloP100		-1.1
BranchPoint Hunter		3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2294016; hg19: chrX-49093528;