1-183945506-C-T

Position:

• chr1-183945506-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015101.4(COLGALT2):​c.1195G>A​(p.Asp399Asn) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: COLGALT2 NM_015101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.59

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLGALT2	NM_015101.4	c.1195G>A	p.Asp399Asn	missense_variant	9/12	ENST00000361927.9
COLGALT2	NM_001303420.2	c.1195G>A	p.Asp399Asn	missense_variant	9/12
COLGALT2	NM_001303421.2	c.835G>A	p.Asp279Asn	missense_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLGALT2	ENST00000361927.9	c.1195G>A	p.Asp399Asn	missense_variant	9/12	1	NM_015101.4	P1
COLGALT2	ENST00000649786.1	c.1195G>A	p.Asp399Asn	missense_variant	9/12
COLGALT2	ENST00000367520.3	c.406G>A	p.Asp136Asn	missense_variant	4/7	2
COLGALT2	ENST00000367521.5	c.19G>A	p.Asp7Asn	missense_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 18, 2023

The c.1195G>A (p.D399N) alteration is located in exon 9 (coding exon 9) of the COLGALT2 gene. This alteration results from a G to A substitution at nucleotide position 1195, causing the aspartic acid (D) at amino acid position 399 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	29
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	1.0	D;D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Uncertain	0.46	D
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.73	T
Polyphen		1.0	.;.;D;D
Vest4		0.65, 0.81, 0.84
MutPred		0.49		Loss of phosphorylation at Y401 (P = 0.0755);.;Loss of phosphorylation at Y401 (P = 0.0755);.;
MVP		0.92
MPC		0.97
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.75
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-183914640;