21-18256794-C-G

Variant names:

• chr21-18256794-C-G
• NM_024944.3:c.365C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024944.3(CHODL):​c.365C>G​(p.Ser122Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHODL NM_024944.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• Publications: 0 publications found

Genes affected

CHODL (HGNC:17807): (chondrolectin) This gene encodes a type I membrane protein with a carbohydrate recognition domain characteristic of C-type lectins in its extracellular portion. In other proteins, this domain is involved in endocytosis of glycoproteins and exogenous sugar-bearing pathogens. This protein localizes predominantly to the perinuclear region. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHODL	NM_024944.3	MANE Select	c.365C>G	p.Ser122Cys	missense	Exon 2 of 6	NP_079220.2
	CHODL	NM_001204174.2		c.308C>G	p.Ser103Cys	missense	Exon 2 of 6	NP_001191103.1	Q9H9P2-4
	CHODL	NM_001204177.2		c.242C>G	p.Ser81Cys	missense	Exon 2 of 5	NP_001191106.1	A0A0C4DFS2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHODL	ENST00000299295.7	TSL:1 MANE Select	c.365C>G	p.Ser122Cys	missense	Exon 2 of 6	ENSP00000299295.2	Q9H9P2-1
	CHODL	ENST00000400131.5	TSL:1	c.242C>G	p.Ser81Cys	missense	Exon 2 of 5	ENSP00000382996.1	A0A0C4DFS2
	CHODL	ENST00000400135.5	TSL:1	c.242C>G	p.Ser81Cys	missense	Exon 3 of 6	ENSP00000383001.1	A0A0C4DFS2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.74		Loss of disorder (P = 0.0024)
MVP		0.59
MPC		0.34
ClinPred		0.98	D
GERP RS		5.7
PromoterAI		-0.014	Neutral
Varity_R		0.21
gMVP		0.55
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

hg19: chr21-19629111;