Variant 1-183944314-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015101.4(COLGALT2):c.1279C>G(p.Arg427Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

COLGALT2
NM_015101.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Variant links:

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]

COLGALT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
COLGALT2	NM_015101.4 linkuse as main transcript	c.1279C>G	p.Arg427Gly	missense_variant	10/12	ENST00000361927.9
COLGALT2	NM_001303420.2 linkuse as main transcript	c.1279C>G	p.Arg427Gly	missense_variant	10/12
COLGALT2	NM_001303421.2 linkuse as main transcript	c.919C>G	p.Arg307Gly	missense_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COLGALT2	ENST00000361927.9 linkuse as main transcript	c.1279C>G	p.Arg427Gly	missense_variant	10/12	1	NM_015101.4	P1
COLGALT2	ENST00000649786.1 linkuse as main transcript	c.1279C>G	p.Arg427Gly	missense_variant	10/12
COLGALT2	ENST00000367520.3 linkuse as main transcript	c.490C>G	p.Arg164Gly	missense_variant	5/7	2
COLGALT2	ENST00000367521.5 linkuse as main transcript	c.103C>G	p.Arg35Gly	missense_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248562

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1459776

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.1279C>G (p.R427G) alteration is located in exon 10 (coding exon 10) of the COLGALT2 gene. This alteration results from a C to G substitution at nucleotide position 1279, causing the arginine (R) at amino acid position 427 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

Benign

0.17

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Uncertain

0.15

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.51

Polyphen

0.99, 0.98

.;.;D;D

Vest4

0.74, 0.75, 0.72

MutPred

0.53

Gain of catalytic residue at E428 (P = 0.1299);.;Gain of catalytic residue at E428 (P = 0.1299);.;

MVP

0.89

MPC

0.55

ClinPred

0.97

GERP RS

4.1

Varity_R

0.58

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over