Genetic Variant B4GALNT2:p.Gly9Val (chr17-49133051-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153446.3(B4GALNT2):c.26G>T(p.Gly9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

B4GALNT2
NM_153446.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.160

Variant links:

Genes affected

B4GALNT2 (HGNC:24136): (beta-1,4-N-acetyl-galactosaminyltransferase 2 (SID blood group)) B4GALNT2 catalyzes the last step in the biosynthesis of the human Sd(a) antigen through the addition of an N-acetylgalactosamine residue via a beta-1,4 linkage to a subterminal galactose residue substituted with an alpha-2,3-linked sialic acid. B4GALNT2 also catalyzes the last step in the biosynthesis of the Cad antigen (Montiel et al., 2003 [PubMed 12678917]).[supplied by OMIM, Mar 2008]

B4GALNT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT2	NM_001159387.2 link	c.14+245G>T		intron_variant	Intron 1 of 10	ENST00000393354.7	NP_001152859.1	Q8NHY0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
B4GALNT2	ENST00000300404.2 link	c.26G>T	p.Gly9Val	missense_variant	Exon 1 of 11	1		ENSP00000300404.2	Q8NHY0-1
B4GALNT2	ENST00000393354.7 link	c.14+245G>T		intron_variant	Intron 1 of 10	1	NM_001159387.2	ENSP00000377022.3	Q8NHY0-2
B4GALNT2	ENST00000504681.5 link	c.-65+541G>T		intron_variant	Intron 1 of 10	2		ENSP00000425510.1	Q8NHY0-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

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:

0.000193

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

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1347252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664784

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

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:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.7

DANN

Benign

0.92

DEOGEN2

Benign

0.052

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.36

M_CAP

Benign

0.0023

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.39

REVEL

Benign

0.056

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.21

MutPred

0.45

Gain of sheet (P = 0.0125);

MVP

0.56

MPC

0.72

ClinPred

0.27

GERP RS

1.6

Varity_R

0.094

gMVP

0.079

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.58

Position offset: -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

Computational scores

Splicing

Publications

LitVar

Other links and lift over