X-49249149-T-C

Variant names:

• chrX-49249149-T-C
• rs2294021
• NM_014008.5:c.1540-18T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_014008.5(CCDC22):​c.1540-18T>C 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 0.51 (10557 hom., 16860 hem., cov: 24)
  • Exomes 𝑓: 0.57 (120278 hom. 201744 hem.)
  • Failed GnomAD Quality Control
• Consequence: CCDC22 NM_014008.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.97
• Publications: 47 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: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-49249149-T-C is Benign according to our data. Variant chrX-49249149-T-C is described in ClinVar as Benign. ClinVar VariationId is 284920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC22	NM_014008.5	MANE Select	c.1540-18T>C		intron	N/A	NP_054727.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC22	ENST00000376227.4	TSL:1 MANE Select	c.1540-18T>C		intron	N/A	ENSP00000365401.3

Frequencies

GnomAD3 genomes AF: 0.508 AC: 56780 AN: 111703 Hom.: 10555 Cov.: 24

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.506

GnomAD2 exomes AF: 0.522 AC: 91508 AN: 175177 AF XY: 0.535

Gnomad AFR exome AF: 0.411

Gnomad AMR exome AF: 0.407

Gnomad ASJ exome AF: 0.578

Gnomad EAS exome AF: 0.391

Gnomad FIN exome AF: 0.513

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.532

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.572 AC: 618923 AN: 1082239 Hom.: 120278 Cov.: 28 AF XY: 0.577 AC XY: 201744 AN XY: 349721

African (AFR) AF: 0.407 AC: 10632 AN: 26118

American (AMR) AF: 0.413 AC: 14377 AN: 34852

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 11259 AN: 19251

East Asian (EAS) AF: 0.396 AC: 11912 AN: 30101

South Asian (SAS) AF: 0.581 AC: 31114 AN: 53529

European-Finnish (FIN) AF: 0.510 AC: 20433 AN: 40072

Middle Eastern (MID) AF: 0.572 AC: 2349 AN: 4105

European-Non Finnish (NFE) AF: 0.593 AC: 491512 AN: 828677

Other (OTH) AF: 0.556 AC: 25335 AN: 45534

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.508 AC: 56814 AN: 111755 Hom.: 10557 Cov.: 24 AF XY: 0.496 AC XY: 16860 AN XY: 33981

African (AFR) AF: 0.408 AC: 12581 AN: 30803

American (AMR) AF: 0.441 AC: 4719 AN: 10689

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 1538 AN: 2646

East Asian (EAS) AF: 0.384 AC: 1344 AN: 3501

South Asian (SAS) AF: 0.574 AC: 1559 AN: 2718

European-Finnish (FIN) AF: 0.491 AC: 2967 AN: 6046

Middle Eastern (MID) AF: 0.576 AC: 125 AN: 217

European-Non Finnish (NFE) AF: 0.583 AC: 30846 AN: 52923

Other (OTH) AF: 0.510 AC: 786 AN: 1541

Alfa AF: 0.547 Hom.: 56000

Bravo AF: 0.498

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Dec 07, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Ritscher-Schinzel syndrome 2 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.76
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2294021; hg19: chrX-49105610; COSMIC: COSV66050798; COSMIC: COSV66050798;