17-49133084-G-T

Variant names:

• chr17-49133084-G-T
• rs761987918
• ENST00000300404.2:c.59G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153446.3(B4GALNT2):​c.59G>T​(p.Arg20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000956 in 1,360,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. R20Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: B4GALNT2 NM_153446.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055199087).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT2	NM_001159387.2	MANE Select	c.14+278G>T		intron	N/A	NP_001152859.1	Q8NHY0-2
	B4GALNT2	NM_153446.3		c.59G>T	p.Arg20Leu	missense	Exon 1 of 11	NP_703147.2	Q8NHY0-1
	B4GALNT2	NM_001159388.2		c.-65+574G>T		intron	N/A	NP_001152860.1	Q8NHY0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALNT2	ENST00000300404.2	TSL:1	c.59G>T	p.Arg20Leu	missense	Exon 1 of 11	ENSP00000300404.2	Q8NHY0-1
	B4GALNT2	ENST00000393354.7	TSL:1 MANE Select	c.14+278G>T		intron	N/A	ENSP00000377022.3	Q8NHY0-2
	B4GALNT2	ENST00000954078.1		c.14+278G>T		intron	N/A	ENSP00000624137.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000956 AC: 13 AN: 1360006 Hom.: 0 Cov.: 74 AF XY: 0.0000119 AC XY: 8 AN XY: 672470

African (AFR) AF: 0.00 AC: 0 AN: 26406

American (AMR) AF: 0.00 AC: 0 AN: 22436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22540

East Asian (EAS) AF: 0.00 AC: 0 AN: 32110

South Asian (SAS) AF: 0.00 AC: 0 AN: 72492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 0.0000121 AC: 13 AN: 1070430

Other (OTH) AF: 0.00 AC: 0 AN: 55746

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.1
DANN	Benign	0.94
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.016
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.15	B
Vest4		0.070
MutPred		0.38		Loss of disorder (P = 0.0179)
MVP		0.21
MPC		0.30
ClinPred		0.072	T
GERP RS		-2.3
PromoterAI		0.090	Neutral
Varity_R		0.075
gMVP		0.27

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

Other links and lift over

dbSNP: rs761987918; hg19: chr17-47210446;