chr19-19541217-C-A

Variant names:

• chr19-19541217-C-A
• NM_153221.2:c.563C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153221.2(CILP2):​c.563C>A​(p.Ala188Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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: 1.06

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13790345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CILP2	NM_153221.2	c.563C>A	p.Ala188Glu	missense_variant	Exon 4 of 8	ENST00000291495.5	NP_694953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CILP2	ENST00000291495.5	c.563C>A	p.Ala188Glu	missense_variant	Exon 4 of 8	1	NM_153221.2	ENSP00000291495.3
CILP2	ENST00000586018.5	c.581C>A	p.Ala194Glu	missense_variant	Exon 4 of 8	2		ENSP00000467413.1
CILP2	ENST00000588333.2	n.253C>A		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1129242 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 539862

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

Jul 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.563C>A (p.A188E) 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 563, causing the alanine (A) at amino acid position 188 to be replaced by a glutamic acid (E). 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	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.063	.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	.;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	.;N
REVEL	Benign	0.065
Sift	Benign	0.46	.;T
Sift4G	Benign	0.079	T;T
Polyphen		0.13	.;B
Vest4		0.37
MutPred		0.54		.;Loss of loop (P = 0.0203);
MVP		0.56
MPC		0.79
ClinPred		0.31	T
GERP RS		3.0
Varity_R		0.22
gMVP		0.44

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: chr19-19652026;