Variant chr17-49159170-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001159387.2(B4GALNT2):c.632A>G(p.His211Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,614,126 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 1 hom. )

Consequence

B4GALNT2
NM_001159387.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20322031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GALNT2	NM_001159387.2 linkuse as main transcript	c.632A>G	p.His211Arg	missense_variant	6/11	ENST00000393354.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALNT2	ENST00000393354.7 linkuse as main transcript	c.632A>G	p.His211Arg	missense_variant	6/11	1	NM_001159387.2	P1	Q8NHY0-2
B4GALNT2	ENST00000300404.2 linkuse as main transcript	c.812A>G	p.His271Arg	missense_variant	6/11	1			Q8NHY0-1
B4GALNT2	ENST00000504681.5 linkuse as main transcript	c.554A>G	p.His185Arg	missense_variant	6/11	2			Q8NHY0-3

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251476

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000380

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:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000330

AC:

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 16, 2022

The c.812A>G (p.H271R) alteration is located in exon 6 (coding exon 6) of the B4GALNT2 gene. This alteration results from a A to G substitution at nucleotide position 812, causing the histidine (H) at amino acid position 271 to be replaced by an arginine (R). 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

0.30

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.19

.;.;T

Eigen

Benign

0.0071

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

.;.;M

MutationTaster

Benign

0.80

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.077

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.25, 1.0

.;B;D

Vest4

0.46

MutPred

0.41

.;.;Gain of MoRF binding (P = 0.012);

MVP

0.64

MPC

0.71

ClinPred

0.059

GERP RS

5.1

Varity_R

0.14

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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