Variant chr1-183945493-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015101.4(COLGALT2):c.1208C>T(p.Ser403Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000535 in 1,614,208 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

COLGALT2
NM_015101.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24344319).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COLGALT2	NM_015101.4 linkuse as main transcript	c.1208C>T	p.Ser403Phe	missense_variant	9/12	ENST00000361927.9
COLGALT2	NM_001303420.2 linkuse as main transcript	c.1208C>T	p.Ser403Phe	missense_variant	9/12
COLGALT2	NM_001303421.2 linkuse as main transcript	c.848C>T	p.Ser283Phe	missense_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COLGALT2	ENST00000361927.9 linkuse as main transcript	c.1208C>T	p.Ser403Phe	missense_variant	9/12	1	NM_015101.4	P1
COLGALT2	ENST00000649786.1 linkuse as main transcript	c.1208C>T	p.Ser403Phe	missense_variant	9/12
COLGALT2	ENST00000367520.3 linkuse as main transcript	c.419C>T	p.Ser140Phe	missense_variant	4/7	2
COLGALT2	ENST00000367521.5 linkuse as main transcript	c.32C>T	p.Ser11Phe	missense_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000489

AC:

123

AN:

251390

Hom.:

AF XY:

0.000523

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000549

AC:

802

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

386

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000609

Gnomad4 OTH exome

AF:

0.000828

GnomAD4 genome

AF:

0.000407

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000543

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.00136

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 02, 2021

The c.1208C>T (p.S403F) alteration is located in exon 9 (coding exon 9) of the COLGALT2 gene. This alteration results from a C to T substitution at nucleotide position 1208, causing the serine (S) at amino acid position 403 to be replaced by a phenylalanine (F). 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

0.20

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Uncertain

0.048

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

Polyphen

0.97, 0.98

.;.;D;D

Vest4

0.37, 0.42, 0.43

MVP

0.88

MPC

0.96

ClinPred

0.087

GERP RS

5.4

Varity_R

0.44

gMVP

0.75

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