chr21-18256794-C-G

Position:

• chr21-18256794-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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	Protein	UniProt
CHODL	NM_024944.3	c.365C>G	p.Ser122Cys	missense_variant	2/6	ENST00000299295.7	NP_079220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHODL	ENST00000299295.7	c.365C>G	p.Ser122Cys	missense_variant	2/6	1	NM_024944.3	ENSP00000299295.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Dec 10, 2024

The c.365C>G (p.S122C) alteration is located in exon 2 (coding exon 2) of the CHODL gene. This alteration results from a C to G substitution at nucleotide position 365, causing the serine (S) at amino acid position 122 to be replaced by a cysteine (C). 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	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;T;.;T;.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;.;.;D;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.5	.;.;.;.;H;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.2	N;N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.025	D;D;D;D;D;D;D
Sift4G	Uncertain	0.041	D;T;T;D;D;D;T
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
Varity_R		0.21
gMVP		0.55

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: chr21-19629111;