chr1-183940777-T-C

Position:

• chr1-183940777-T-C

Variant summary

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

The NM_015101.4(COLGALT2):​c.1408A>G​(p.Arg470Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COLGALT2 NM_015101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLGALT2	NM_015101.4	c.1408A>G	p.Arg470Gly	missense_variant	11/12	ENST00000361927.9
COLGALT2	NM_001303420.2	c.1408A>G	p.Arg470Gly	missense_variant	11/12
COLGALT2	NM_001303421.2	c.1048A>G	p.Arg350Gly	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLGALT2	ENST00000361927.9	c.1408A>G	p.Arg470Gly	missense_variant	11/12	1	NM_015101.4	P1
COLGALT2	ENST00000649786.1	c.1408A>G	p.Arg470Gly	missense_variant	11/12
COLGALT2	ENST00000367520.3	c.619A>G	p.Arg207Gly	missense_variant	6/7	2
COLGALT2	ENST00000367521.5	c.232A>G	p.Arg78Gly	missense_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Dec 28, 2022

The c.1408A>G (p.R470G) alteration is located in exon 11 (coding exon 11) of the COLGALT2 gene. This alteration results from a A to G substitution at nucleotide position 1408, causing the arginine (R) at amino acid position 470 to be replaced by a glycine (G). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.92	D;D;D;D
MetaSVM	Uncertain	0.34	D
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
Polyphen		1.0	.;.;D;D
Vest4		0.94, 0.92, 0.92
MutPred		0.78		Loss of MoRF binding (P = 0.0506);.;Loss of MoRF binding (P = 0.0506);.;
MVP		0.88
MPC		1.1
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.90
gMVP		0.92

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: chr1-183909911;