1-183938903-T-C

Position:

• chr1-183938903-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_015101.4(COLGALT2):​c.1739A>G​(p.Asn580Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COLGALT2 NM_015101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.75

Genes affected

COLGALT2 (HGNC:16790): (collagen beta(1-O)galactosyltransferase 2) Predicted to enable procollagen galactosyltransferase activity. Predicted to be involved in collagen fibril organization. Predicted to be located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity GT252_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLGALT2	NM_015101.4	c.1739A>G	p.Asn580Ser	missense_variant	12/12	ENST00000361927.9	NP_055916.1
COLGALT2	NM_001303421.2	c.1379A>G	p.Asn460Ser	missense_variant	12/12		NP_001290350.1
COLGALT2	NM_001303420.2	c.1604+1678A>G		intron_variant			NP_001290349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLGALT2	ENST00000361927.9	c.1739A>G	p.Asn580Ser	missense_variant	12/12	1	NM_015101.4	ENSP00000354960.4
COLGALT2	ENST00000367520.3	c.950A>G	p.Asn317Ser	missense_variant	7/7	2		ENSP00000356490.3
COLGALT2	ENST00000367521.5	c.563A>G	p.Asn188Ser	missense_variant	4/4	2		ENSP00000356491.1
COLGALT2	ENST00000649786.1	c.1604+1678A>G		intron_variant				ENSP00000497601.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jul 14, 2024

The c.1739A>G (p.N580S) alteration is located in exon 12 (coding exon 12) of the COLGALT2 gene. This alteration results from a A to G substitution at nucleotide position 1739, causing the asparagine (N) at amino acid position 580 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T;T;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.97	D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.7	D;N;D
REVEL	Uncertain	0.45
Sift	Benign	0.066	T;D;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.98, 0.97	.;D;D
Vest4		0.27
MutPred		0.45		.;Gain of glycosylation at N580 (P = 0.0109);.;
MVP		0.89
MPC		0.50
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.23
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1000353542; hg19: chr1-183908037; COSMIC: COSV100730804;