19-19541201-G-T

Variant names:

• chr19-19541201-G-T
• NM_153221.2:c.547G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_153221.2(CILP2):​c.547G>T​(p.Gly183Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.94

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CILP2	NM_153221.2	c.547G>T	p.Gly183Trp	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.547G>T	p.Gly183Trp	missense_variant	Exon 4 of 8	1	NM_153221.2	ENSP00000291495.3
CILP2	ENST00000586018.5	c.565G>T	p.Gly189Trp	missense_variant	Exon 4 of 8	2		ENSP00000467413.1
CILP2	ENST00000588333.2	n.237G>T		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: 1124938 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 537490

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

Mar 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.547G>T (p.G183W) alteration is located in exon 4 (coding exon 4) of the CILP2 gene. This alteration results from a G to T substitution at nucleotide position 547, causing the glycine (G) at amino acid position 183 to be replaced by a tryptophan (W). 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	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.69	T;T
M_CAP	Pathogenic	0.65	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Pathogenic	4.2	.;H
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.4	.;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0080	.;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	.;D
Vest4		0.73
MutPred		0.78		.;Gain of sheet (P = 0.0344);
MVP		0.73
MPC		1.3
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.55
gMVP		0.80

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: chr19-19652010;