2-179945409-T-A

Variant names:

• chr2-179945409-T-A
• rs747011855
• NM_020943.3:c.2447A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020943.3(CWC22):​c.2447A>T​(p.His816Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H816R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CWC22 NM_020943.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.788
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07095909).

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.2447A>T	p.His816Leu	missense	Exon 20 of 20	NP_065994.1	Q9HCG8
	CWC22	NM_001376029.1		c.2447A>T	p.His816Leu	missense	Exon 20 of 20	NP_001362958.1	Q9HCG8
	CWC22	NM_001376030.1		c.2447A>T	p.His816Leu	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.2447A>T	p.His816Leu	missense	Exon 20 of 20	ENSP00000387006.3	Q9HCG8
	CWC22	ENST00000918074.1		c.2447A>T	p.His816Leu	missense	Exon 20 of 20	ENSP00000588133.1
	CWC22	ENST00000910802.1		c.2441A>T	p.His814Leu	missense	Exon 20 of 20	ENSP00000580861.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.79
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.082
Sift	Uncertain	0.011	D
Sift4G	Benign	0.28	T
Polyphen		0.030	B
Vest4		0.17
MutPred		0.26		Loss of solvent accessibility (P = 0.0172)
MVP		0.12
MPC		0.13
ClinPred		0.094	T
GERP RS		1.2
Varity_R		0.11
gMVP		0.16
Mutation Taster		=94/6	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: rs747011855; hg19: chr2-180810136;