chr2-179945259-C-T

Variant names:

• chr2-179945259-C-T
• rs190476525
• NM_020943.3:c.2597G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020943.3(CWC22):​c.2597G>A​(p.Ser866Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: CWC22 NM_020943.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

Genes affected

CWC22 (HGNC:29322): (CWC22 spliceosome associated protein homolog) Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in cytosol and nuclear speck. Part of U2-type catalytic step 1 spliceosome; U2-type catalytic step 2 spliceosome; and U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0106651485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020943.3. 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
	CWC22	NM_020943.3	MANE Select	c.2597G>A	p.Ser866Asn	missense	Exon 20 of 20	NP_065994.1	Q9HCG8
	CWC22	NM_001376029.1		c.2597G>A	p.Ser866Asn	missense	Exon 20 of 20	NP_001362958.1	Q9HCG8
	CWC22	NM_001376030.1		c.2597G>A	p.Ser866Asn	missense	Exon 20 of 20	NP_001362959.1	Q9HCG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWC22	ENST00000410053.8	TSL:1 MANE Select	c.2597G>A	p.Ser866Asn	missense	Exon 20 of 20	ENSP00000387006.3	Q9HCG8
	CWC22	ENST00000918074.1		c.2597G>A	p.Ser866Asn	missense	Exon 20 of 20	ENSP00000588133.1
	CWC22	ENST00000910802.1		c.2591G>A	p.Ser864Asn	missense	Exon 20 of 20	ENSP00000580861.1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000926 AC: 23 AN: 248506 AF XY: 0.0000816

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461466 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 726994

African (AFR) AF: 0.000986 AC: 33 AN: 33472

American (AMR) AF: 0.0000894 AC: 4 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111768

Other (OTH) AF: 0.0000994 AC: 6 AN: 60366

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74446

African (AFR) AF: 0.00104 AC: 43 AN: 41544

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.000461

ESP6500AA AF: 0.00136 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000993 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.063
Sift	Benign	0.41	T
Sift4G	Benign	0.47	T
Polyphen		0.18	B
Vest4		0.094
MVP		0.14
MPC		0.097
ClinPred		0.014	T
GERP RS		4.3
Varity_R		0.053
gMVP		0.031
Mutation Taster		=92/8	polymorphism

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: rs190476525; hg19: chr2-180809986;