11-107329942-G-C

Variant names:

• chr11-107329942-G-C
• rs769555047
• NM_152434.3:c.2517C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152434.3(CWF19L2):​c.2517C>G​(p.His839Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,590,972 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: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: CWF19L2 NM_152434.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026025236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CWF19L2	NM_152434.3	c.2517C>G	p.His839Gln	missense_variant	Exon 17 of 18	ENST00000282251.10	NP_689647.2
CWF19L2	XM_047426419.1	c.1089C>G	p.His363Gln	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.2517C>G	p.His839Gln	missense_variant	Exon 17 of 18	1	NM_152434.3	ENSP00000282251.5

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.0000863 AC: 19 AN: 220054 AF XY: 0.0000765

Gnomad AFR exome AF: 0.000997

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000511

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000584 AC: 84 AN: 1438836 Hom.: 0 Cov.: 29 AF XY: 0.0000589 AC XY: 42 AN XY: 713530

African (AFR) AF: 0.00161 AC: 53 AN: 32974

American (AMR) AF: 0.0000244 AC: 1 AN: 41058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25588

East Asian (EAS) AF: 0.00 AC: 0 AN: 39018

South Asian (SAS) AF: 0.00 AC: 0 AN: 81674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000236 AC: 26 AN: 1100874

Other (OTH) AF: 0.0000672 AC: 4 AN: 59560

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74320

African (AFR) AF: 0.00111 AC: 46 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.000960 AC: 2 AN: 2084

Alfa AF: 0.000169 Hom.: 0

Bravo AF: 0.000385

ExAC AF: 0.0000248 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2517C>G (p.H839Q) alteration is located in exon 17 (coding exon 17) of the CWF19L2 gene. This alteration results from a C to G substitution at nucleotide position 2517, causing the histidine (H) at amino acid position 839 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.49
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.45	N
PhyloP100		1.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.027
Sift	Benign	0.36	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.35		Gain of ubiquitination at K840 (P = 0.102);
MVP		0.14
MPC		0.015
ClinPred		0.0080	T
GERP RS		1.6
Varity_R		0.27
gMVP		0.44
Mutation Taster		=75/25	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: rs769555047; hg19: chr11-107200668;