Genetic Variant CILP2:p.Trp53Ser (chr19-19539772-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153221.2(CILP2):c.158G>C(p.Trp53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 1,587,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CILP2
NM_153221.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

CILP2 (HGNC:24213): (cartilage intermediate layer protein 2) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CILP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.092607975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CILP2	NM_153221.2 link	c.158G>C	p.Trp53Ser	missense_variant	Exon 2 of 8	ENST00000291495.5	NP_694953.2	Q8IUL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CILP2	ENST00000291495.5 link	c.158G>C	p.Trp53Ser	missense_variant	Exon 2 of 8	1	NM_153221.2	ENSP00000291495.3		Q8IUL8
CILP2	ENST00000586018.5 link	c.158G>C	p.Trp53Ser	missense_variant	Exon 2 of 8	2		ENSP00000467413.1		K7EPJ4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000389

AC:

AN:

231650

Hom.:

AF XY:

0.0000238

AC XY:

AN XY:

126158

show subpopulations

Gnomad AFR exome

AF:

0.000273

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000383

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1434972

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

712046

show subpopulations

Gnomad4 AFR exome

AF:

0.000157

Gnomad4 AMR exome

AF:

0.0000237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000821

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158G>C (p.W53S) alteration is located in exon 2 (coding exon 2) of the CILP2 gene. This alteration results from a G to C substitution at nucleotide position 158, causing the tryptophan (W) at amino acid position 53 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.031

.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.3

.;N

REVEL

Benign

0.16

Sift

Benign

0.54

.;T

Sift4G

Benign

0.34

T;T

Polyphen

0.015

.;B

Vest4

0.45

MVP

0.51

MPC

0.62

ClinPred

0.027

GERP RS

3.5

Varity_R

0.33

gMVP

0.68

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over