NM_020943.3:c.2314T>G

Variant names:

• chr2-179945542-A-C
• NM_020943.3:c.2314T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020943.3(CWC22):​c.2314T>G​(p.Ser772Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,994 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CWC22 NM_020943.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.824
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027236253).

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.2314T>G	p.Ser772Ala	missense	Exon 20 of 20	NP_065994.1	Q9HCG8
	CWC22	NM_001376029.1		c.2314T>G	p.Ser772Ala	missense	Exon 20 of 20	NP_001362958.1	Q9HCG8
	CWC22	NM_001376030.1		c.2314T>G	p.Ser772Ala	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.2314T>G	p.Ser772Ala	missense	Exon 20 of 20	ENSP00000387006.3	Q9HCG8
	CWC22	ENST00000918074.1		c.2314T>G	p.Ser772Ala	missense	Exon 20 of 20	ENSP00000588133.1
	CWC22	ENST00000910802.1		c.2308T>G	p.Ser770Ala	missense	Exon 20 of 20	ENSP00000580861.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460994 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726782

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111458

Other (OTH) AF: 0.00 AC: 0 AN: 60322

GnomAD4 genome Cov.: 31

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	0.061
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.82
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.061
Sift	Benign	0.10	T
Sift4G	Benign	0.78	T
Polyphen		0.14	B
Vest4		0.20
MutPred		0.14		Loss of phosphorylation at S772 (P = 0.02)
MVP		0.085
MPC		0.090
ClinPred		0.10	T
GERP RS		3.6
Varity_R		0.056
gMVP		0.054
Mutation Taster		=99/1	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

hg19: chr2-180810269;