NM_153221.2:c.241C>G

Variant names:

• chr19-19540281-C-G
• NM_153221.2:c.241C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153221.2(CILP2):​c.241C>G​(p.Arg81Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,447,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R81S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CILP2 NM_153221.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CILP2	NM_153221.2	c.241C>G	p.Arg81Gly	missense_variant	Exon 3 of 8	ENST00000291495.5	NP_694953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CILP2	ENST00000291495.5	c.241C>G	p.Arg81Gly	missense_variant	Exon 3 of 8	1	NM_153221.2	ENSP00000291495.3
CILP2	ENST00000586018.5	c.259C>G	p.Arg87Gly	missense_variant	Exon 3 of 8	2		ENSP00000467413.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1447302 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 719684

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: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.9	.;H
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.5	.;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	.;D
Vest4		0.91
MutPred		0.69		.;Gain of catalytic residue at F82 (P = 0.0891);
MVP		0.61
MPC		1.3
ClinPred		1.0	D
GERP RS		3.2
Varity_R		0.75
gMVP		0.89

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: chr19-19651090;