rs147976839

Variant names:

• chr11-107329928-T-C
• rs147976839
• NM_152434.3:c.2531A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-107329928-T-C
• chr11-107329928-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152434.3(CWF19L2):​c.2531A>G​(p.Tyr844Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Y844S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CWF19L2 NM_152434.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.01
• Publications: 0 publications found

Genes affected

CWF19L2 (HGNC:26508): (CWF19 like cell cycle control factor 2) Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be part of post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L2	NM_152434.3	c.2531A>G	p.Tyr844Cys	missense_variant	Exon 17 of 18	ENST00000282251.10	NP_689647.2
CWF19L2	XM_047426419.1	c.1103A>G	p.Tyr368Cys	missense_variant	Exon 10 of 11		XP_047282375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L2	ENST00000282251.10	c.2531A>G	p.Tyr844Cys	missense_variant	Exon 17 of 18	1	NM_152434.3	ENSP00000282251.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1421644 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 704230

African (AFR) AF: 0.00 AC: 0 AN: 32120

American (AMR) AF: 0.00 AC: 0 AN: 36540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24816

East Asian (EAS) AF: 0.00 AC: 0 AN: 38778

South Asian (SAS) AF: 0.00 AC: 0 AN: 78446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094430

Other (OTH) AF: 0.00 AC: 0 AN: 58862

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		8.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.099	T
Polyphen		1.0	D
Vest4		0.92
MutPred		0.64		Loss of ubiquitination at K840 (P = 0.0727);
MVP		0.53
MPC		0.12
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.97
gMVP		0.85
Mutation Taster		=80/20	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: rs147976839; hg19: chr11-107200654;