2-179945720-G-A

Variant names:

• chr2-179945720-G-A
• rs139376109
• NM_020943.3:c.2141-5C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020943.3(CWC22):​c.2141-5C>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 0.00974 in 1,499,382 control chromosomes in the GnomAD database, including 112 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (14 hom., cov: 31)
  • Exomes 𝑓: 0.0099 (98 hom.)
• Consequence: CWC22 NM_020943.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001781
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-179945720-G-A is Benign according to our data. Variant chr2-179945720-G-A is described in ClinVar as [Benign]. Clinvar id is 3898103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWC22	NM_020943.3	c.2141-5C>T		splice_region_variant, intron_variant	Intron 19 of 19	ENST00000410053.8	NP_065994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWC22	ENST00000410053.8	c.2141-5C>T		splice_region_variant, intron_variant	Intron 19 of 19	1	NM_020943.3	ENSP00000387006.3
CWC22	ENST00000404136.2	c.2141-5C>T		splice_region_variant, intron_variant	Intron 19 of 19	1		ENSP00000384159.2

Frequencies

GnomAD3 genomes AF: 0.00810 AC: 1230 AN: 151892 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.00223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.00576

GnomAD3 exomes AF: 0.00803 AC: 1670 AN: 208020 Hom.: 11 AF XY: 0.00807 AC XY: 920 AN XY: 114026

Gnomad AFR exome AF: 0.00151

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00130

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000413

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.00791

GnomAD4 exome AF: 0.00993 AC: 13376 AN: 1347372 Hom.: 98 Cov.: 22 AF XY: 0.00972 AC XY: 6555 AN XY: 674132

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00316

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.000230

Gnomad4 SAS exome AF: 0.0000257

Gnomad4 FIN exome AF: 0.0221

Gnomad4 NFE exome AF: 0.0113

Gnomad4 OTH exome AF: 0.00814

GnomAD4 genome AF: 0.00809 AC: 1230 AN: 152010 Hom.: 14 Cov.: 31 AF XY: 0.00896 AC XY: 666 AN XY: 74294

Gnomad4 AFR AF: 0.00222

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0277

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00570

Alfa AF: 0.00955 Hom.: 0

Bravo AF: 0.00603

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000018
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: rs139376109; hg19: chr2-180810447;