rs2294020

Variant names:

• chrX-49246763-A-G
• rs2294020
• NM_014008.5:c.747A>G
• CCDC22 p.Gln249Gln

Your query was ambiguous. Multiple possible variants found:

• chrX-49246763-A-G
• chrX-49246763-A-C
• chrX-49246763-A-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_014008.5(CCDC22):​c.747A>G​(p.Gln249Gln) variant causes a synonymous 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 (15335 hom., 20559 hem., cov: 24)
  • Exomes 𝑓: 0.69 (175068 hom. 236243 hem.)
  • Failed GnomAD Quality Control
• Consequence: CCDC22 NM_014008.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.164
• Publications: 27 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, ClinGen, Labcorp Genetics (formerly Invitae), 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant X-49246763-A-G is Benign according to our data. Variant chrX-49246763-A-G is described in ClinVar as Benign. ClinVar VariationId is 769177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.164 with no splicing effect.

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.747A>G	p.Gln249Gln	synonymous	Exon 7 of 17	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.747A>G	p.Gln249Gln	synonymous	Exon 7 of 17	ENSP00000365401.3	O60826
	CCDC22	ENST00000960401.1		c.771A>G	p.Gln257Gln	synonymous	Exon 7 of 17	ENSP00000630460.1
	CCDC22	ENST00000904959.1		c.765A>G	p.Gln255Gln	synonymous	Exon 7 of 17	ENSP00000575018.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 68218 AN: 111928 Hom.: 15335 Cov.: 24

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.620

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.694 AC: 734524 AN: 1059082 Hom.: 175068 Cov.: 38 AF XY: 0.698 AC XY: 236243 AN XY: 338646

African (AFR) AF: 0.435 AC: 10993 AN: 25274

American (AMR) AF: 0.470 AC: 14174 AN: 30181

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 13677 AN: 17454

East Asian (EAS) AF: 0.397 AC: 11665 AN: 29369

South Asian (SAS) AF: 0.691 AC: 33754 AN: 48862

European-Finnish (FIN) AF: 0.648 AC: 24371 AN: 37633

Middle Eastern (MID) AF: 0.711 AC: 2651 AN: 3728

European-Non Finnish (NFE) AF: 0.722 AC: 593548 AN: 822351

Other (OTH) AF: 0.671 AC: 29691 AN: 44230

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.609 AC: 68250 AN: 111978 Hom.: 15335 Cov.: 24 AF XY: 0.602 AC XY: 20559 AN XY: 34176

African (AFR) AF: 0.443 AC: 13677 AN: 30880

American (AMR) AF: 0.532 AC: 5703 AN: 10711

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2105 AN: 2643

East Asian (EAS) AF: 0.391 AC: 1364 AN: 3492

South Asian (SAS) AF: 0.668 AC: 1845 AN: 2760

European-Finnish (FIN) AF: 0.642 AC: 3884 AN: 6054

Middle Eastern (MID) AF: 0.697 AC: 152 AN: 218

European-Non Finnish (NFE) AF: 0.720 AC: 38154 AN: 53025

Other (OTH) AF: 0.621 AC: 944 AN: 1519

Alfa AF: 0.660 Hom.: 29395

Bravo AF: 0.590

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	1.5
PhyloP100		0.16

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2294020;

hg19: chrX-49103224;