X-49246636-A-T

Variant names:

• chrX-49246636-A-T
• rs2294019
• NM_014008.5:c.715-95A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014008.5(CCDC22):​c.715-95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (15176 hom., 19838 hem., cov: 23)
  • Exomes 𝑓: 0.70 (122015 hom. 121619 hem.)
  • Failed GnomAD Quality Control
• Consequence: CCDC22 NM_014008.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.186
• Publications: 4 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-49246636-A-T is Benign according to our data. Variant chrX-49246636-A-T is described in ClinVar as [Benign]. Clinvar id is 3911558.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC22	NM_014008.5	c.715-95A>T		intron_variant	Intron 6 of 16	ENST00000376227.4	NP_054727.1
CCDC22	XM_005272599.5	c.712-95A>T		intron_variant	Intron 6 of 16		XP_005272656.1
CCDC22	XR_430506.4	n.882-95A>T		intron_variant	Intron 6 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4	c.715-95A>T		intron_variant	Intron 6 of 16	1	NM_014008.5	ENSP00000365401.3

Frequencies

GnomAD3 genomes AF: 0.605 AC: 67188 AN: 110963 Hom.: 15177 Cov.: 23

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.614

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.705 AC: 463812 AN: 657948 Hom.: 122015 AF XY: 0.715 AC XY: 121619 AN XY: 170214

African (AFR) AF: 0.442 AC: 6816 AN: 15422

American (AMR) AF: 0.509 AC: 6726 AN: 13202

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 9003 AN: 11810

East Asian (EAS) AF: 0.399 AC: 9526 AN: 23862

South Asian (SAS) AF: 0.697 AC: 19581 AN: 28110

European-Finnish (FIN) AF: 0.649 AC: 21497 AN: 33135

Middle Eastern (MID) AF: 0.736 AC: 1385 AN: 1882

European-Non Finnish (NFE) AF: 0.737 AC: 368704 AN: 500092

Other (OTH) AF: 0.676 AC: 20574 AN: 30433

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.605 AC: 67216 AN: 111016 Hom.: 15176 Cov.: 23 AF XY: 0.596 AC XY: 19838 AN XY: 33278

African (AFR) AF: 0.434 AC: 13263 AN: 30578

American (AMR) AF: 0.531 AC: 5622 AN: 10587

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2026 AN: 2627

East Asian (EAS) AF: 0.385 AC: 1336 AN: 3466

South Asian (SAS) AF: 0.670 AC: 1783 AN: 2660

European-Finnish (FIN) AF: 0.635 AC: 3779 AN: 5949

Middle Eastern (MID) AF: 0.704 AC: 152 AN: 216

European-Non Finnish (NFE) AF: 0.718 AC: 37887 AN: 52732

Other (OTH) AF: 0.615 AC: 937 AN: 1523

Alfa AF: 0.649 Hom.: 5087

Bravo AF: 0.586

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: 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	-0.88
CADD	Benign	0.19
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs2294019; hg19: chrX-49103097;