Genetic Variant GXYLT2:p.Ile175Val (chr3-72922258-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080393.2(GXYLT2):c.523A>G(p.Ile175Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,613,394 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 232 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 185 hom. )

Consequence

GXYLT2
NM_001080393.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.60

Variant links:

Genes affected

GXYLT2 (HGNC:33383): (glucoside xylosyltransferase 2) The protein encoded by this gene is a xylosyltransferase that elongates O-linked glucose bound to epidermal growth factor (EGF) repeats. The encoded protein catalyzes the addition of xylose to the O-glucose-modified residues of EGF repeats of Notch proteins. [provided by RefSeq, Sep 2016]

GXYLT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002999127).

BP6

Variant 3-72922258-A-G is Benign according to our data. Variant chr3-72922258-A-G is described in ClinVar as [Benign]. Clinvar id is 775201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GXYLT2	NM_001080393.2 link	c.523A>G	p.Ile175Val	missense_variant	Exon 3 of 7	ENST00000389617.9	NP_001073862.1	A0PJZ3
GXYLT2	NR_138564.2 link	n.711A>G		non_coding_transcript_exon_variant	Exon 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GXYLT2	ENST00000389617.9 link	c.523A>G	p.Ile175Val	missense_variant	Exon 3 of 7	5	NM_001080393.2	ENSP00000374268.4		A0PJZ3
GXYLT2	ENST00000498315.1 link	c.145A>G	p.Ile49Val	missense_variant	Exon 2 of 3	2		ENSP00000417239.1		C9J3Q6

Frequencies

GnomAD3 genomes

AF:

0.0300

AC:

4558

AN:

152076

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.00763

AC:

1902

AN:

249118

Hom.:

AF XY:

0.00575

AC XY:

777

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.00508

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00306

AC:

4478

AN:

1461200

Hom.:

185

Cov.:

AF XY:

0.00274

AC XY:

1990

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.00626

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000302

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.00704

GnomAD4 genome

AF:

0.0301

AC:

4577

AN:

152194

Hom.:

232

Cov.:

AF XY:

0.0294

AC XY:

2189

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.00582

Hom.:

Bravo

AF:

0.0345

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0963

AC:

359

ESP6500EA

AF:

0.000486

AC:

ExAC

AF:

0.00951

AC:

1149

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;D

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.17

Sift

Benign

0.13

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.70

P;.

Vest4

0.52

MVP

0.54

MPC

0.60

ClinPred

0.041

GERP RS

5.8

Varity_R

0.11

gMVP

0.48

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