Genetic Variant B4GALNT2:p.Gln116Pro (chr17-49142166-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001159387.2(B4GALNT2):c.347A>C(p.Gln116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q116R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

B4GALNT2
NM_001159387.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159387.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALNT2	NM_001159387.2	MANE Select	c.347A>C	p.Gln116Pro	missense	Exon 3 of 11	NP_001152859.1	Q8NHY0-2
B4GALNT2	NM_153446.3		c.527A>C	p.Gln176Pro	missense	Exon 3 of 11	NP_703147.2	Q8NHY0-1
B4GALNT2	NM_001159388.2		c.269A>C	p.Gln90Pro	missense	Exon 3 of 11	NP_001152860.1	Q8NHY0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B4GALNT2	ENST00000393354.7	TSL:1 MANE Select	c.347A>C	p.Gln116Pro	missense	Exon 3 of 11	ENSP00000377022.3	Q8NHY0-2
B4GALNT2	ENST00000300404.2	TSL:1	c.527A>C	p.Gln176Pro	missense	Exon 3 of 11	ENSP00000300404.2	Q8NHY0-1
B4GALNT2	ENST00000954078.1		c.347A>C	p.Gln116Pro	missense	Exon 3 of 12	ENSP00000624137.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251394

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.77

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

PhyloP100

2.7

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.19

Sift

Benign

0.068

Sift4G

Benign

0.076

Polyphen

1.0

Vest4

0.80

MutPred

0.27

Gain of catalytic residue at Q176 (P = 0.0543)

MVP

0.72

MPC

0.72

ClinPred

0.97

GERP RS

4.4

Varity_R

0.66

gMVP

0.84

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over