19-19540464-C-G

Position:

• chr19-19540464-C-G

Variant summary

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

The NM_153221.2(CILP2):​c.424C>G​(p.Arg142Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,249,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CILP2 NM_153221.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07

Genes affected

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

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=0.27181122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CILP2	NM_153221.2	c.424C>G	p.Arg142Gly	missense_variant	3/8	ENST00000291495.5	NP_694953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CILP2	ENST00000291495.5	c.424C>G	p.Arg142Gly	missense_variant	3/8	1	NM_153221.2	ENSP00000291495.3
CILP2	ENST00000586018.5	c.442C>G	p.Arg148Gly	missense_variant	3/8	2		ENSP00000467413.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000104 AC: 13 AN: 1249376 Hom.: 0 Cov.: 35 AF XY: 0.00000823 AC XY: 5 AN XY: 607318

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: 0.0000129

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Aug 04, 2023

The c.424C>G (p.R142G) alteration is located in exon 3 (coding exon 3) of the CILP2 gene. This alteration results from a C to G substitution at nucleotide position 424, causing the arginine (R) at amino acid position 142 to be replaced by a glycine (G). 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	0.47
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.1	.;N
REVEL	Benign	0.064
Sift	Benign	0.10	.;T
Sift4G	Benign	0.11	T;T
Polyphen		0.028	.;B
Vest4		0.39
MutPred		0.44		.;Loss of MoRF binding (P = 0.0269);
MVP		0.38
MPC		0.68
ClinPred		0.82	D
GERP RS		2.9
Varity_R		0.40
gMVP		0.56

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: chr19-19651273;