Variant chr19-19541204-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153221.2(CILP2):c.550C>A(p.Arg184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,276,660 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 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CILP2
NM_153221.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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:

CILP2 (HGNC:):

CILP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0671837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CILP2	NM_153221.2 linkuse as main transcript	c.550C>A	p.Arg184Ser	missense_variant	4/8	ENST00000291495.5	NP_694953.2	Q8IUL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CILP2	ENST00000291495.5 linkuse as main transcript	c.550C>A	p.Arg184Ser	missense_variant	4/8	1	NM_153221.2	ENSP00000291495.3	Q8IUL8
CILP2	ENST00000586018.5 linkuse as main transcript	c.568C>A	p.Arg190Ser	missense_variant	4/8	2		ENSP00000467413.1	K7EPJ4
CILP2	ENST00000588333.2 linkuse as main transcript	n.240C>A		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1124514

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

537028

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000149

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:

0.00000106

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.00000877

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2024

The c.550C>A (p.R184S) alteration is located in exon 4 (coding exon 4) of the CILP2 gene. This alteration results from a C to A substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 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

0.19

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.099

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.18

.;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.035

Sift

Benign

0.79

.;T

Sift4G

Benign

0.51

T;T

Polyphen

0.050

.;B

Vest4

0.17

MutPred

0.39

.;Gain of glycosylation at R184 (P = 0.0049);

MVP

0.43

MPC

0.46

ClinPred

0.066

GERP RS

3.0

Varity_R

0.10

gMVP

0.51

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