rs191605685

Positions:

• chrX-49243277-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014008.5(CCDC22):​c.536-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,197,339 control chromosomes in the GnomAD database, including 13 homozygotes. There are 1,853 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., 106 hem., cov: 23)
  • Exomes 𝑓: 0.0048 (13 hom. 1747 hem.)
• Consequence: CCDC22 NM_014008.5 splice_region, intron
• Scores: Splicing: ADA: 0.00002202
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.159

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant X-49243277-C-T is Benign according to our data. Variant chrX-49243277-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-49243277-C-T is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 106 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC22	NM_014008.5	c.536-7C>T		splice_region_variant, intron_variant		ENST00000376227.4	NP_054727.1
CCDC22	XM_005272599.5	c.533-7C>T		splice_region_variant, intron_variant			XP_005272656.1
CCDC22	XR_430506.4	n.703-7C>T		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC22	ENST00000376227.4	c.536-7C>T		splice_region_variant, intron_variant		1	NM_014008.5	ENSP00000365401.3
CCDC22	ENST00000490300.1	n.679-7C>T		splice_region_variant, intron_variant		3
CCDC22	ENST00000496651.5	n.627-7C>T		splice_region_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 374 AN: 112639 Hom.: 0 Cov.: 23 AF XY: 0.00305 AC XY: 106 AN XY: 34797

Gnomad AFR AF: 0.000904

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00214

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00366

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00837

Gnomad NFE AF: 0.00541

Gnomad OTH AF: 0.00265

GnomAD3 exomes AF: 0.00363 AC: 584 AN: 160921 Hom.: 2 AF XY: 0.00413 AC XY: 201 AN XY: 48687

Gnomad AFR exome AF: 0.000665

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.000630

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00449

Gnomad FIN exome AF: 0.00248

Gnomad NFE exome AF: 0.00600

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00479 AC: 5192 AN: 1084645 Hom.: 13 Cov.: 31 AF XY: 0.00497 AC XY: 1747 AN XY: 351855

Gnomad4 AFR exome AF: 0.000305

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.000694

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00526

Gnomad4 FIN exome AF: 0.00258

Gnomad4 NFE exome AF: 0.00545

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00333 AC: 375 AN: 112694 Hom.: 0 Cov.: 23 AF XY: 0.00304 AC XY: 106 AN XY: 34862

Gnomad4 AFR AF: 0.000902

Gnomad4 AMR AF: 0.00213

Gnomad4 ASJ AF: 0.00113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00404

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00541

Gnomad4 OTH AF: 0.00261

Alfa AF: 0.00465 Hom.: 38

Bravo AF: 0.00260

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 07, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jan 14, 2019	- -

Ritscher-Schinzel syndrome 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.48
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs191605685; hg19: chrX-49099743;