rs199528550

Variant names:

• chr11-107336620-T-A
• rs199528550
• NM_152434.3:c.2296A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-107336620-T-A
• chr11-107336620-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152434.3(CWF19L2):​c.2296A>T​(p.Met766Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. M766V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CWF19L2 NM_152434.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.93
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41859788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L2	NM_152434.3	c.2296A>T	p.Met766Leu	missense_variant	Exon 15 of 18	ENST00000282251.10	NP_689647.2
CWF19L2	XM_047426419.1	c.868A>T	p.Met290Leu	missense_variant	Exon 8 of 11		XP_047282375.1
CWF19L2	XR_007062452.1	n.*7A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CWF19L2	ENST00000282251.10	c.2296A>T	p.Met766Leu	missense_variant	Exon 15 of 18	1	NM_152434.3	ENSP00000282251.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455390 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723912

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 43912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.00 AC: 0 AN: 84884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108758

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0017
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.98	L
PhyloP100		3.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.16
Sift	Benign	0.13	T
Sift4G	Benign	0.27	T
Polyphen		0.049	B
Vest4		0.57
MutPred		0.52		Loss of methylation at K761 (P = 0.055);
MVP		0.17
MPC		0.016
ClinPred		0.53	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.52
gMVP		0.73
Mutation Taster		=84/16	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: rs199528550; hg19: chr11-107207346;