chr1-111231255-T-A

Position:

• chr1-111231255-T-A

Variant summary

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

The NM_004000.3(CHI3L2):​c.290T>A​(p.Ile97Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHI3L2 NM_004000.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

Genes affected

CHI3L2 (HGNC:1933): (chitinase 3 like 2) The protein encoded by this gene is similar to bacterial chitinases but lacks chitinase activity. The encoded protein is secreted and is involved in cartilage biogenesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHI3L2	NM_004000.3	c.290T>A	p.Ile97Asn	missense_variant	4/11	ENST00000369748.9
CHI3L2	NM_001025197.1	c.260T>A	p.Ile87Asn	missense_variant	3/10
CHI3L2	NM_001025199.2	c.53T>A	p.Ile18Asn	missense_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHI3L2	ENST00000369748.9	c.290T>A	p.Ile97Asn	missense_variant	4/11	1	NM_004000.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

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

Feb 28, 2023

The c.290T>A (p.I97N) alteration is located in exon 4 (coding exon 4) of the CHI3L2 gene. This alteration results from a T to A substitution at nucleotide position 290, causing the isoleucine (I) at amino acid position 97 to be replaced by an asparagine (N). 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	0.33
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.044	T;.;T;.;T;T;.;.;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.86	.;D;D;T;T;D;.;D;T;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;.;.;L;.;.;.;.;.
MutationTaster	Benign	0.88	D;D;D;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.070	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.096
Sift	Uncertain	0.024	D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.023	D;D;D;D;D;D;D;D;D;D
Polyphen		0.93	P;.;.;.;P;.;.;.;.;.
Vest4		0.78
MutPred		0.86		Gain of disorder (P = 0.0193);Gain of disorder (P = 0.0193);Gain of disorder (P = 0.0193);.;Gain of disorder (P = 0.0193);Gain of disorder (P = 0.0193);.;.;.;.;
MVP		0.57
MPC		0.062
ClinPred		0.63	D
GERP RS		2.5
Varity_R		0.67
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-111773877;