Variant 1-183939033-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015101.4(COLGALT2):c.1609G>A(p.Glu537Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,608,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

COLGALT2
NM_015101.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061851233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COLGALT2	NM_015101.4 linkuse as main transcript	c.1609G>A	p.Glu537Lys	missense_variant	12/12	ENST00000361927.9
COLGALT2	NM_001303421.2 linkuse as main transcript	c.1249G>A	p.Glu417Lys	missense_variant	12/12
COLGALT2	NM_001303420.2 linkuse as main transcript	c.1604+1548G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COLGALT2	ENST00000361927.9 linkuse as main transcript	c.1609G>A	p.Glu537Lys	missense_variant	12/12	1	NM_015101.4	P1
COLGALT2	ENST00000367520.3 linkuse as main transcript	c.820G>A	p.Glu274Lys	missense_variant	7/7	2
COLGALT2	ENST00000367521.5 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	4/4	2
COLGALT2	ENST00000649786.1 linkuse as main transcript	c.1604+1548G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

250108

Hom.:

AF XY:

0.0000740

AC XY:

AN XY:

135108

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000975

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000124

AC:

181

AN:

1456028

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

723014

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.000118

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

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 16, 2022

The c.1609G>A (p.E537K) alteration is located in exon 12 (coding exon 12) of the COLGALT2 gene. This alteration results from a G to A substitution at nucleotide position 1609, causing the glutamic acid (E) at amino acid position 537 to be replaced by a lysine (K). 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

0.069

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.062

T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0080, 0.0060

.;B;B

Vest4

0.068

MVP

0.67

MPC

0.33

ClinPred

0.034

GERP RS

4.2

Varity_R

0.13

gMVP

0.63

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

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