Variant 1-183944315-A-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.1278T>A(p.Asp426Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

COLGALT2
NM_015101.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.411

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=0.042660654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COLGALT2	NM_015101.4 linkuse as main transcript	c.1278T>A	p.Asp426Glu	missense_variant	10/12	ENST00000361927.9
COLGALT2	NM_001303420.2 linkuse as main transcript	c.1278T>A	p.Asp426Glu	missense_variant	10/12
COLGALT2	NM_001303421.2 linkuse as main transcript	c.918T>A	p.Asp306Glu	missense_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COLGALT2	ENST00000361927.9 linkuse as main transcript	c.1278T>A	p.Asp426Glu	missense_variant	10/12	1	NM_015101.4	P1
COLGALT2	ENST00000649786.1 linkuse as main transcript	c.1278T>A	p.Asp426Glu	missense_variant	10/12
COLGALT2	ENST00000367520.3 linkuse as main transcript	c.489T>A	p.Asp163Glu	missense_variant	5/7	2
COLGALT2	ENST00000367521.5 linkuse as main transcript	c.102T>A	p.Asp34Glu	missense_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

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:

0.000192

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:

0.0000402

AC:

AN:

248942

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000233

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1460124

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

726326

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000245

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74472

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:

0.0000113

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

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

Aug 15, 2023

The c.1278T>A (p.D426E) alteration is located in exon 10 (coding exon 10) of the COLGALT2 gene. This alteration results from a T to A substitution at nucleotide position 1278, causing the aspartic acid (D) at amino acid position 426 to be replaced by a glutamic acid (E). 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

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.5

DANN

Benign

0.53

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.67

T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.043

T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.56

D;D;D;D

PrimateAI

Benign

0.37

Polyphen

0.019, 0.0030

.;.;B;B

Vest4

0.095, 0.094

MutPred

0.34

Gain of ubiquitination at K431 (P = 0.1317);.;Gain of ubiquitination at K431 (P = 0.1317);.;

MVP

0.51

MPC

0.28

ClinPred

0.011

GERP RS

0.66

Varity_R

0.066

gMVP

0.35

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