rs146090744

Positions:

chr1-235484480-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152490.5(B3GALNT2):c.397G>A(p.Glu133Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000378 in 1,614,120 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00040 ( 12 hom. )

Consequence

B3GALNT2
NM_152490.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.26

Variant links:

Genes affected

B3GALNT2 (HGNC:28596): (beta-1,3-N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 31 family. The encoded protein synthesizes GalNAc:beta-1,3GlcNAc, a novel carbohydrate structure, on N- and O-glycans. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2013]

B3GALNT2 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=0.0055506527).

BP6

Variant 1-235484480-C-T is Benign according to our data. Variant chr1-235484480-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235484480-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000204 (31/152262) while in subpopulation SAS AF= 0.00518 (25/4826). AF 95% confidence interval is 0.0036. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
B3GALNT2	NM_152490.5 linkuse as main transcript	c.397G>A	p.Glu133Lys	missense_variant	4/12	ENST00000366600.8	NP_689703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B3GALNT2	ENST00000366600.8 linkuse as main transcript	c.397G>A	p.Glu133Lys	missense_variant	4/12	1	NM_152490.5	ENSP00000355559	P1	Q8NCR0-1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000705

AC:

177

AN:

251164

Hom.:

AF XY:

0.000987

AC XY:

134

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000396

AC:

579

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

411

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00568

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000204

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000791

AC:

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	B3GALNT2: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2018	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

B3GALNT2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 05, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.023

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.84

D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.082

Sift

Benign

0.12

T;.

Sift4G

Benign

0.27

T;T

Polyphen

0.74

P;D

Vest4

0.57

MVP

0.61

MPC

0.37

ClinPred

0.061

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.34

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