chr19-19541204-C-T

Position:

• chr19-19541204-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153221.2(CILP2):​c.550C>T​(p.Arg184Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CILP2 NM_153221.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

Genes affected

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

CILP2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39938703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CILP2	NM_153221.2	c.550C>T	p.Arg184Cys	missense_variant	4/8	ENST00000291495.5	NP_694953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CILP2	ENST00000291495.5	c.550C>T	p.Arg184Cys	missense_variant	4/8	1	NM_153221.2	ENSP00000291495.3
CILP2	ENST00000586018.5	c.568C>T	p.Arg190Cys	missense_variant	4/8	2		ENSP00000467413.1
CILP2	ENST00000588333.2	n.240C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1124516 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 537030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.550C>T (p.R184C) alteration is located in exon 4 (coding exon 4) of the CILP2 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 to be replaced by a cysteine (C). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.28	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.1	.;D
REVEL	Benign	0.17
Sift	Benign	0.062	.;T
Sift4G	Uncertain	0.054	T;T
Polyphen		1.0	.;D
Vest4		0.34
MutPred		0.60		.;Gain of sheet (P = 0.0221);
MVP		0.64
MPC		1.3
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.11
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19652013; COSMIC: COSV52280955; COSMIC: COSV52280955;